36 results on '"Muriana, Arantza"'
Search Results
2. Implementation of Zebrafish Ontologies for Toxicology Screening
- Author
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Thessen, Anne E, Marvel, Skylar, Achenbach, JC, Fischer, Stephan, Haendel, Melissa A, Hayward, Kimberly, Klüver, Nils, Könemann, Sarah, Legradi, Jessica, Lein, Pamela, Leong, Connor, Mylroie, J Erik, Padilla, Stephanie, Perone, Dante, Planchart, Antonio, Prieto, Rafael Miñana, Muriana, Arantza, Quevedo, Celia, Reif, David, Ryan, Kristen, Stinckens, Evelyn, Truong, Lisa, Vergauwen, Lucia, Berg, Colette Vom, Wilbanks, Mitch, Yaghoobi, Bianca, and Hamm, Jon
- Subjects
Biological Sciences ,Health Sciences ,Genetics ,Danio rerio ,annotation ,endpoint ,ontology ,phenotype ,zebrafish - Abstract
Toxicological evaluation of chemicals using early-life stage zebrafish (Danio rerio) involves the observation and recording of altered phenotypes. Substantial variability has been observed among researchers in phenotypes reported from similar studies, as well as a lack of consistent data annotation, indicating a need for both terminological and data harmonization. When examined from a data science perspective, many of these apparent differences can be parsed into the same or similar endpoints whose measurements differ only in time, methodology, or nomenclature. Ontological knowledge structures can be leveraged to integrate diverse data sets across terminologies, scales, and modalities. Building on this premise, the National Toxicology Program's Systematic Evaluation of the Application of Zebrafish in Toxicology undertook a collaborative exercise to evaluate how the application of standardized phenotype terminology improved data consistency. To accomplish this, zebrafish researchers were asked to assess images of zebrafish larvae for morphological malformations in two surveys. In the first survey, researchers were asked to annotate observed malformations using their own terminology. In the second survey, researchers were asked to annotate the images from a list of terms and definitions from the Zebrafish Phenotype Ontology. Analysis of the results suggested that the use of ontology terms increased consistency and decreased ambiguity, but a larger study is needed to confirm. We conclude that utilizing a common data standard will not only reduce the heterogeneity of reported terms but increases agreement and repeatability between different laboratories. Thus, we advocate for the development of a zebrafish phenotype atlas to help laboratories create interoperable, computable data.
- Published
- 2022
3. Applications of Zebrafish Embryo Models to Predict Developmental Toxicity for Agrochemical Product Development.
- Author
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Bianchi, Enrica, Bhattacharya, Beas, Bowling, Andrew J., Pence, Heather E., Mundy, Paige C., Jones, Gabe, Muriana, Arantza, Grever, William E., Pappas-Garton, Anthony, Sriram, Shreedharan, LaRocca, Jessica, and Bondesson, Maria
- Published
- 2024
- Full Text
- View/download PDF
4. Interlaboratory Study on Zebrafish in Toxicology: Systematic Evaluation of the Application of Zebrafish in Toxicology’s (SEAZIT’s) Evaluation of Developmental Toxicity
- Author
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Hamm, Jon T., primary, Hsieh, Jui-Hua, additional, Roberts, Georgia K., additional, Collins, Bradley, additional, Gorospe, Jenni, additional, Sparrow, Barney, additional, Walker, Nigel J., additional, Truong, Lisa, additional, Tanguay, Robyn L., additional, Dyballa, Sylvia, additional, Miñana, Rafael, additional, Schiavone, Valentina, additional, Terriente, Javier, additional, Weiner, Andrea, additional, Muriana, Arantza, additional, Quevedo, Celia, additional, and Ryan, Kristen R., additional
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- 2024
- Full Text
- View/download PDF
5. Implementation of Zebrafish Ontologies for Toxicology Screening
- Author
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Thessen, Anne E., primary, Marvel, Skylar, additional, Achenbach, J. C., additional, Fischer, Stephan, additional, Haendel, Melissa A., additional, Hayward, Kimberly, additional, Klüver, Nils, additional, Könemann, Sarah, additional, Legradi, Jessica, additional, Lein, Pamela, additional, Leong, Connor, additional, Mylroie, J. Erik, additional, Padilla, Stephanie, additional, Perone, Dante, additional, Planchart, Antonio, additional, Prieto, Rafael Miñana, additional, Muriana, Arantza, additional, Quevedo, Celia, additional, Reif, David, additional, Ryan, Kristen, additional, Stinckens, Evelyn, additional, Truong, Lisa, additional, Vergauwen, Lucia, additional, Vom Berg, Colette, additional, Wilbanks, Mitch, additional, Yaghoobi, Bianca, additional, and Hamm, Jon, additional
- Published
- 2022
- Full Text
- View/download PDF
6. An inter-laboratory case study to determine the added value of the Zebrafish Light-dark transition test to predict developmental neurotoxicity: Report from OECD DNT Expert Group
- Author
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Hessel, Ellen, Shafer, Timothy, Padilla, Stephanie, Hill, Bridgett, Truong, Lisa, Tanguay, Robyn L., Hsieh, Jui-Hua, Ryan, Kristen, Behl, Mamta, Ellis, Lee, Schiavone, Valentina, Rubbini, Davide, Terriente, Javier, Alzualde, Ainhoa, Muriana, Arantza, Legradi, Jessica, Woodland, Cindy, Sachana, Magdalini, Price, Anna, and Klüver, Nils
- Subjects
Toxicology (incl. clinical toxicology) - Abstract
Presentation to the Society of Toxicology 2021 Virtual Annual Meeting March 2021 Search for CCTE records in EPA’s Science Inventory by typing in the title at this link. https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25
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- 2022
- Full Text
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7. An Inter-laboratory Case Study to Harmonize Zebrafish Light-Dark Transition Test to Predict Developmental Neurotoxicity (WC11)
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Muriana, Arantza, Alzualde, Ainhoa, Hsieh, Jui-Hua, Ryan, Kristen, Behl, Mamta, Terron, Andrea, Woodland, Cindy, Kl��ver, Nils, Hessel, Ellen, Ellis, Lee, Truong, Lisa, Tanguay, Robyn L., Sachana, Magdalini, Hill, Bridgett, Padilla, Stephanie, Shafer, Timothy, Legradi, Jessica, Schiavone, Valentina, Rubbini, Davide, Di Donato, Vincenzo, and Terriente, Javier
- Subjects
Toxicology - Abstract
Presentation to the 11th World Congress on Alternative and Animal Use in the Life Sciences August 2021Search for CCTE records in EPA���s Science Inventory by typing in the title at this link.https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25
- Published
- 2022
- Full Text
- View/download PDF
8. An inter-laboratory case study to determine the added value of the Zebrafish Light-dark transition test to predict developmental neurotoxicity
- Author
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Alzualde, Ainhoa, Hsieh, Jui-Hua, Ellis, Lee, Schiavone, Valentina, Truong, Lisa, Legradi, Jessica, Rubbini, Davide, Woodland, Cindy, Kl��ver, Nils, Ryan, Kristen, Behl, Mamta, Terriente, Javier, Muriana, Arantza, Tanguay, Robyn L., Sachana, Magdalini, Price, Anna, Hill, Bridgett, Padilla, Stephanie, Shafer, Timothy, and Hessel, Ellen
- Subjects
Toxicology - Abstract
Poster presented to the European Society of Environmental Toxicology and Chemistry (SETAC) meeting May 2021Search for CCTE records in EPA���s Science Inventory by typing in the title at this link.https://cfpub.epa.gov/si/si_public_search_results.cfm?advSearch=true&showCriteria=2&keyword=CCTE&TIMSType=&TIMSSubTypeID=&epaNumber=&ombCat=Any&dateBeginPublishedPresented=07/01/2017&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&DEID=&personName=&personID=&role=Any&journalName=&journalID=&publisherName=&publisherID=&sortBy=pubDate&count=25
- Published
- 2021
- Full Text
- View/download PDF
9. Screening of multi-endocrine disruptors in zebrafish
- Author
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Iturria, Iñaki, primary, Martí, Celia, additional, Jaka, Oihane, additional, Muriana, Arantza, additional, and Mazón, María José, additional
- Published
- 2021
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10. Alternatives to Animal Use in Risk Assessment of Mixtures
- Author
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Wallace Hayes, A., primary, Muriana, Arantza, additional, Alzualde, Ainhoa, additional, Fernandez, Dania Bacardi, additional, Iskandar, Anita, additional, Peitsch, Manuel C., additional, Kuczaj, Arkadiusz, additional, and Hoeng, Julia, additional
- Published
- 2020
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11. Thyroid Disruption Screening Using Zebrafish as a Vertebrate Model
- Author
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Iturria, Iñaki, Jaka, Oihane, Martí, Celia, Alzualde, Ainhoa, and Muriana, Arantza
- Published
- 2018
- Full Text
- View/download PDF
12. Use of Zebrafish in Drug Discovery Toxicology
- Author
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Cassar, Steven, primary, Adatto, Isaac, additional, Freeman, Jennifer L., additional, Gamse, Joshua T., additional, Iturria, Iñaki, additional, Lawrence, Christian, additional, Muriana, Arantza, additional, Peterson, Randall T., additional, Van Cruchten, Steven, additional, and Zon, Leonard I., additional
- Published
- 2019
- Full Text
- View/download PDF
13. Detection and Prioritization of Developmentally Neurotoxic and/or Neurotoxic Compounds Using Zebrafish
- Author
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Quevedo, Celia, primary, Behl, Mamta, additional, Ryan, Kristen, additional, Paules, Richard S, additional, Alday, Aintzane, additional, Muriana, Arantza, additional, and Alzualde, Ainhoa, additional
- Published
- 2018
- Full Text
- View/download PDF
14. Toxicity profiling of flame retardants in zebrafish embryos using a battery of assays for developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity toward human relevance
- Author
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Alzualde, Ainhoa, primary, Behl, Mamta, additional, Sipes, Nisha S., additional, Hsieh, Jui-Hua, additional, Alday, Aintzane, additional, Tice, Raymond R., additional, Paules, Richard S., additional, Muriana, Arantza, additional, and Quevedo, Celia, additional
- Published
- 2018
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- View/download PDF
15. Automated Morphological Feature Assessment for Zebrafish Embryo Developmental Toxicity Screens
- Author
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Teixidó, Elisabet, primary, Kießling, Tobias R, additional, Krupp, Eckart, additional, Quevedo, Celia, additional, Muriana, Arantza, additional, and Scholz, Stefan, additional
- Published
- 2018
- Full Text
- View/download PDF
16. Zebrafish and Medaka as Alternative Models for Developmental Toxicity Assessment of Chemicals (Including Behavior as An End Point)
- Author
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Quevedo, Celia, primary, De Croze, Noémie, additional, Alday, Aintzane, additional, Muriana, Arantza, additional, and Léonard, Marc, additional
- Published
- 2018
- Full Text
- View/download PDF
17. Developmental toxicity assessment of thalidomide and its derivatives lenalidomide and pomalidomide in zebrafish embryos
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González, Izaskun, primary, Ipiñazar, Maitane, additional, Muriana, Arantza, additional, and Quevedo, Celia, additional
- Published
- 2018
- Full Text
- View/download PDF
18. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
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Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Bhatia, Sangeeta N, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Yesmalie, Alemán Resto, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria Belen, Ken, Chih-Chien Cheng, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Bhatia, Sangeeta N, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Yesmalie, Alemán Resto, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria Belen, Ken, Chih-Chien Cheng, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2017
19. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
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Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.
- Published
- 2016
20. Use of Zebrafish in Drug Discovery Toxicology
- Author
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Cassar, Steven, Adatto, Isaac, Freeman, Jennifer L., Gamse, Joshua T., Iturria, Iñaki, Lawrence, Christian, Muriana, Arantza, Peterson, Randall T., Van Cruchten, Steven, and Zon, Leonard I.
- Abstract
Unpredicted human safety events in clinical trials for new drugs are costly in terms of human health and money. The drug discovery industry attempts to minimize those events with diligent preclinical safety testing. Current standard practices are good at preventing toxic compounds from being tested in the clinic; however, false negative preclinical toxicity results are still a reality. Continual improvement must be pursued in the preclinical realm. Higher-quality therapies can be brought forward with more information about potential toxicities and associated mechanisms. The zebrafish model is a bridge between in vitro assays and mammalian in vivo studies. This model is powerful in its breadth of application and tractability for research. In the past two decades, our understanding of disease biology and drug toxicity has grown significantly owing to thousands of studies on this tiny vertebrate. This Review summarizes challenges and strengths of the model, discusses the 3Rs value that it can deliver, highlights translatable and untranslatable biology, and brings together reports from recent studies with zebrafish focusing on new drug discovery toxicology.
- Published
- 2020
- Full Text
- View/download PDF
21. Detection and Prioritization of Developmentally Neurotoxic and/or Neurotoxic Compounds Using Zebrafish.
- Author
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Quevedo, Celia, Behl, Mamta, Ryan, Kristen, Paules, Richard S, Alday, Aintzane, Muriana, Arantza, and Alzualde, Ainhoa
- Subjects
NEUROTOXIC agents ,LOGPERCH ,EMBRYOS ,HUMAN abnormalities ,MUSCULOSKELETAL system - Abstract
The standard methods for toxicity testing using rodent models cannot keep pace with the increasing number of chemicals in our environment due to time and resource limitations. Hence, there is an unmet need for fast, sensitive, and cost-effective alternate models to reliably predict toxicity. As part of Tox21 Phase III's effort, a 90-compound library was created and made available to researchers to screen for neurotoxicants using novel technology and models. The chemical library was evaluated in zebrafish in a dose-range finding test for embryo-toxicity (ie, mortality or morphological alterations induced by each chemical). In addition, embryos exposed to the lowest effect level and nonobservable effect level were used to measure the internal concentration of the chemicals within the embryos by bioanalysis. Finally, considering the lowest effect level as the highest testing concentration, a functional assay was performed based on locomotor activity alteration in response to light-dark changes. The quality control chemicals included in the library, ie, negative controls and replicated chemicals, indicate that the assays performed were reliable. The use of analytical chemistry pointed out the importance of measuring chemical concentration inside embryos, and in particular, in the case of negative chemicals to avoid false negative classification. Overall, the proposed approach presented a good sensitivity and supports the inclusion of zebrafish assays as a reliable, relevant, and efficient screening tool to identify, prioritize, and evaluate chemical toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
22. Automated Morphological Feature Assessment for Zebrafish Embryo Developmental Toxicity Screens.
- Author
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Teixidó, Elisabet, Kießling, Tobias R, Krupp, Eckart, Quevedo, Celia, Muriana, Arantza, and Scholz, Stefan
- Subjects
ZEBRA danio embryos ,ALTERNATIVE toxicity testing ,MORPHOMETRICS ,IMAGE analysis ,DEVELOPMENTAL toxicology ,SCIENTIFIC software - Abstract
Detection of developmental phenotypes in zebrafish embryos typically involves a visual assessment and scoring of morphological features by an individual researcher. Subjective scoring could impact results and be of particular concern when phenotypic effect patterns are also used as a diagnostic tool to classify compounds. Here we introduce a quantitative morphometric approach based on image analysis of zebrafish embryos. A software called FishInspector was developed to detect morphological features from images collected using an automated system to position zebrafish embryos. The analysis was verified and compared with visual assessments of 3 participating laboratories using 3 known developmental toxicants (methotrexate, dexamethasone, and topiramate) and 2 negative compounds (loratadine and glibenclamide). The quantitative approach exhibited higher sensitivity and made it possible to compare patterns of effects with the potential to establish a grouping and classification of developmental toxicants. Our approach improves the robustness of phenotype scoring and reliability of assay performance and, hence, is anticipated to improve the predictivity of developmental toxicity screening using the zebrafish embryo. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
23. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
-
Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2016
- Full Text
- View/download PDF
24. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
-
Biochemistry, Center for Drug Discovery, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Biochemistry, Center for Drug Discovery, Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Resto, Yesmalie Aleman, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Juergen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Cassera, Maria B., Cheng, Ken Chih-Chien, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colon-Lopez, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, El-Sayed, Shimaa Abd El-Salam, Ferdig, Michael T., Robledo, Jose A. Fernandez, Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Javier Gamo, Francisco, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, van Huijsduijnen, Rob Hooft, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Jensen, Amornrat Naranuntarat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Jose Lafuente, Maria, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinas, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Vera, Iset Medina, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Rodrigues da Costa, Francielly Morais, Mueller, Joachim, Muriana, Arantza, Hewitt, Stephen Nakazawa, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Ngoc Pham, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Rizk, Mohamed Abdo, Ruecker, Andrea, St Onge, Robert, Ferreira, Rafaela Salgado, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Villela, Filipe Silva, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmueller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William G., Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Phat Voong Vinh, Hoan Vu, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoit, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Published
- 2016
25. Assessing cardiotoxicity in the zebrafish embryo
- Author
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Alzualde, Ainhoa, primary, Holgado, Olaia, additional, Bertran, Enric, additional, Geiter-Wilke, Andrea, additional, Muriana, Arantza, additional, and Roberts, Sonia, additional
- Published
- 2016
- Full Text
- View/download PDF
26. Testing toxicity of graphene oxide in zebrafish embryos
- Author
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Quevedo, Celia, primary, Hernández, Frank J., additional, Irijalba, Itziar, additional, and Muriana, Arantza, additional
- Published
- 2016
- Full Text
- View/download PDF
27. An inter-laboratory validation of the zebrafish embryo assay for the detection of developmental toxicity
- Author
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Teixidó, Elisabet, primary, Leuthold, David, additional, Scholz, Stefan, additional, Quevedo, Celia, additional, Muriana, Arantza, additional, Czich, Andreas, additional, and Krupp, Eckart, additional
- Published
- 2016
- Full Text
- View/download PDF
28. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond
- Author
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Van Voorhis, Wesley C., primary, Adams, John H., additional, Adelfio, Roberto, additional, Ahyong, Vida, additional, Akabas, Myles H., additional, Alano, Pietro, additional, Alday, Aintzane, additional, Alemán Resto, Yesmalie, additional, Alsibaee, Aishah, additional, Alzualde, Ainhoa, additional, Andrews, Katherine T., additional, Avery, Simon V., additional, Avery, Vicky M., additional, Ayong, Lawrence, additional, Baker, Mark, additional, Baker, Stephen, additional, Ben Mamoun, Choukri, additional, Bhatia, Sangeeta, additional, Bickle, Quentin, additional, Bounaadja, Lotfi, additional, Bowling, Tana, additional, Bosch, Jürgen, additional, Boucher, Lauren E., additional, Boyom, Fabrice F., additional, Brea, Jose, additional, Brennan, Marian, additional, Burton, Audrey, additional, Caffrey, Conor R., additional, Camarda, Grazia, additional, Carrasquilla, Manuela, additional, Carter, Dee, additional, Belen Cassera, Maria, additional, Chih-Chien Cheng, Ken, additional, Chindaudomsate, Worathad, additional, Chubb, Anthony, additional, Colon, Beatrice L., additional, Colón-López, Daisy D., additional, Corbett, Yolanda, additional, Crowther, Gregory J., additional, Cowan, Noemi, additional, D’Alessandro, Sarah, additional, Le Dang, Na, additional, Delves, Michael, additional, DeRisi, Joseph L., additional, Du, Alan Y., additional, Duffy, Sandra, additional, Abd El-Salam El-Sayed, Shimaa, additional, Ferdig, Michael T., additional, Fernández Robledo, José A., additional, Fidock, David A., additional, Florent, Isabelle, additional, Fokou, Patrick V. T., additional, Galstian, Ani, additional, Gamo, Francisco Javier, additional, Gokool, Suzanne, additional, Gold, Ben, additional, Golub, Todd, additional, Goldgof, Gregory M., additional, Guha, Rajarshi, additional, Guiguemde, W. Armand, additional, Gural, Nil, additional, Guy, R. Kiplin, additional, Hansen, Michael A. E., additional, Hanson, Kirsten K., additional, Hemphill, Andrew, additional, Hooft van Huijsduijnen, Rob, additional, Horii, Takaaki, additional, Horrocks, Paul, additional, Hughes, Tyler B., additional, Huston, Christopher, additional, Igarashi, Ikuo, additional, Ingram-Sieber, Katrin, additional, Itoe, Maurice A., additional, Jadhav, Ajit, additional, Naranuntarat Jensen, Amornrat, additional, Jensen, Laran T., additional, Jiang, Rays H. Y., additional, Kaiser, Annette, additional, Keiser, Jennifer, additional, Ketas, Thomas, additional, Kicka, Sebastien, additional, Kim, Sunyoung, additional, Kirk, Kiaran, additional, Kumar, Vidya P., additional, Kyle, Dennis E., additional, Lafuente, Maria Jose, additional, Landfear, Scott, additional, Lee, Nathan, additional, Lee, Sukjun, additional, Lehane, Adele M., additional, Li, Fengwu, additional, Little, David, additional, Liu, Liqiong, additional, Llinás, Manuel, additional, Loza, Maria I., additional, Lubar, Aristea, additional, Lucantoni, Leonardo, additional, Lucet, Isabelle, additional, Maes, Louis, additional, Mancama, Dalu, additional, Mansour, Nuha R., additional, March, Sandra, additional, McGowan, Sheena, additional, Medina Vera, Iset, additional, Meister, Stephan, additional, Mercer, Luke, additional, Mestres, Jordi, additional, Mfopa, Alvine N., additional, Misra, Raj N., additional, Moon, Seunghyun, additional, Moore, John P., additional, Morais Rodrigues da Costa, Francielly, additional, Müller, Joachim, additional, Muriana, Arantza, additional, Nakazawa Hewitt, Stephen, additional, Nare, Bakela, additional, Nathan, Carl, additional, Narraidoo, Nathalie, additional, Nawaratna, Sujeevi, additional, Ojo, Kayode K., additional, Ortiz, Diana, additional, Panic, Gordana, additional, Papadatos, George, additional, Parapini, Silvia, additional, Patra, Kailash, additional, Pham, Ngoc, additional, Prats, Sarah, additional, Plouffe, David M., additional, Poulsen, Sally-Ann, additional, Pradhan, Anupam, additional, Quevedo, Celia, additional, Quinn, Ronald J., additional, Rice, Christopher A., additional, Abdo Rizk, Mohamed, additional, Ruecker, Andrea, additional, St. Onge, Robert, additional, Salgado Ferreira, Rafaela, additional, Samra, Jasmeet, additional, Robinett, Natalie G., additional, Schlecht, Ulrich, additional, Schmitt, Marjorie, additional, Silva Villela, Filipe, additional, Silvestrini, Francesco, additional, Sinden, Robert, additional, Smith, Dennis A., additional, Soldati, Thierry, additional, Spitzmüller, Andreas, additional, Stamm, Serge Maximilian, additional, Sullivan, David J., additional, Sullivan, William, additional, Suresh, Sundari, additional, Suzuki, Brian M., additional, Suzuki, Yo, additional, Swamidass, S. Joshua, additional, Taramelli, Donatella, additional, Tchokouaha, Lauve R. Y., additional, Theron, Anjo, additional, Thomas, David, additional, Tonissen, Kathryn F., additional, Townson, Simon, additional, Tripathi, Abhai K., additional, Trofimov, Valentin, additional, Udenze, Kenneth O., additional, Ullah, Imran, additional, Vallieres, Cindy, additional, Vigil, Edgar, additional, Vinetz, Joseph M., additional, Voong Vinh, Phat, additional, Vu, Hoan, additional, Watanabe, Nao-aki, additional, Weatherby, Kate, additional, White, Pamela M., additional, Wilks, Andrew F., additional, Winzeler, Elizabeth A., additional, Wojcik, Edward, additional, Wree, Melanie, additional, Wu, Wesley, additional, Yokoyama, Naoaki, additional, Zollo, Paul H. A., additional, Abla, Nada, additional, Blasco, Benjamin, additional, Burrows, Jeremy, additional, Laleu, Benoît, additional, Leroy, Didier, additional, Spangenberg, Thomas, additional, Wells, Timothy, additional, and Willis, Paul A., additional
- Published
- 2016
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- View/download PDF
29. Toxicity profiling of flame retardants in zebrafish embryos using a battery of assays for teratogenicity, behavior, cardiotoxicity, and hepatotoxicity
- Author
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Alzualde, Ainhoa, primary, Alday, Aintzane, additional, Behl, Mamta, additional, Tice, Raymond R., additional, Paules, Richard S., additional, Irijalba, Itziar, additional, Holgado, Olaia, additional, Muriana, Arantza, additional, and Quevedo, Celia, additional
- Published
- 2015
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- View/download PDF
30. Targeted Identification of Sialoglycoproteins in Hypoxic Endothelial Cells and Validation in Zebrafish Reveal Roles for Proteins in Angiogenesis
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Delcourt, Nicolas, primary, Quevedo, Celia, additional, Nonne, Christelle, additional, Fons, Pierre, additional, O'Brien, Donogh, additional, Loyaux, Denis, additional, Diez, Maria, additional, Autelitano, François, additional, Guillemot, Jean-Claude, additional, Ferrara, Pascual, additional, Muriana, Arantza, additional, Callol, Carlos, additional, Hérault, Jean-Pascal, additional, Herbert, Jean-Marc, additional, Favre, Gilles, additional, and Bono, Françoise, additional
- Published
- 2015
- Full Text
- View/download PDF
31. Screening of compounds that alter sleep–wake state in zebrafish
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Holgado, Olaia, primary, Muriana, Arantza, additional, Dekeyne, Anne, additional, Louis, Caroline, additional, and Alzualde, Ainhoa, additional
- Published
- 2014
- Full Text
- View/download PDF
32. Open source drug discovery with the malaria box compound collection for neglected diseases and beyond
- Author
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Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D'Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H. Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R. Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-Aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Subjects
3. Good health
33. Open source drug discovery with the Malaria Box Compound collection for neglected diseases and beyond
- Author
-
Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Full Text
- View/download PDF
34. Open source drug discovery with the Malaria Box Compound collection for neglected diseases and beyond
- Author
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Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Full Text
- View/download PDF
35. Open source drug discovery with the Malaria Box Compound collection for neglected diseases and beyond
- Author
-
Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Full Text
- View/download PDF
36. Open source drug discovery with the Malaria Box Compound collection for neglected diseases and beyond
- Author
-
Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, Willis, Paul A., Phillips, Margaret A., Van Voorhis, Wesley C., Adams, John H., Adelfio, Roberto, Ahyong, Vida, Akabas, Myles H., Alano, Pietro, Alday, Aintzane, Alemán Resto, Yesmalie, Alsibaee, Aishah, Alzualde, Ainhoa, Andrews, Katherine T., Avery, Simon V., Avery, Vicky M., Ayong, Lawrence, Baker, Mark, Baker, Stephen, Ben Mamoun, Choukri, Bhatia, Sangeeta, Bickle, Quentin, Bounaadja, Lotfi, Bowling, Tana, Bosch, Jürgen, Boucher, Lauren E., Boyom, Fabrice F., Brea, Jose, Brennan, Marian, Burton, Audrey, Caffrey, Conor R., Camarda, Grazia, Carrasquilla, Manuela, Carter, Dee, Belen Cassera, Maria, Chih-Chien Cheng, Ken, Chindaudomsate, Worathad, Chubb, Anthony, Colon, Beatrice L., Colón-López, Daisy D., Corbett, Yolanda, Crowther, Gregory J., Cowan, Noemi, D’Alessandro, Sarah, Le Dang, Na, Delves, Michael, DeRisi, Joseph L., Du, Alan Y., Duffy, Sandra, Abd El-Salam El-Sayed, Shimaa, Ferdig, Michael T., Fernández Robledo, José A., Fidock, David A., Florent, Isabelle, Fokou, Patrick V. T., Galstian, Ani, Gamo, Francisco Javier, Gokool, Suzanne, Gold, Ben, Golub, Todd, Goldgof, Gregory M., Guha, Rajarshi, Guiguemde, W. Armand, Gural, Nil, Guy, R. Kiplin, Hansen, Michael A. E., Hanson, Kirsten K., Hemphill, Andrew, Hooft van Huijsduijnen, Rob, Horii, Takaaki, Horrocks, Paul, Hughes, Tyler B., Huston, Christopher, Igarashi, Ikuo, Ingram-Sieber, Katrin, Itoe, Maurice A., Jadhav, Ajit, Naranuntarat Jensen, Amornrat, Jensen, Laran T., Jiang, Rays H.Y., Kaiser, Annette, Keiser, Jennifer, Ketas, Thomas, Kicka, Sebastien, Kim, Sunyoung, Kirk, Kiaran, Kumar, Vidya P., Kyle, Dennis E., Lafuente, Maria Jose, Landfear, Scott, Lee, Nathan, Lee, Sukjun, Lehane, Adele M., Li, Fengwu, Little, David, Liu, Liqiong, Llinás, Manuel, Loza, Maria I., Lubar, Aristea, Lucantoni, Leonardo, Lucet, Isabelle, Maes, Louis, Mancama, Dalu, Mansour, Nuha R., March, Sandra, McGowan, Sheena, Medina Vera, Iset, Meister, Stephan, Mercer, Luke, Mestres, Jordi, Mfopa, Alvine N., Misra, Raj N., Moon, Seunghyun, Moore, John P., Morais Rodrigues da Costa, Francielly, Müller, Joachim, Muriana, Arantza, Nakazawa Hewitt, Stephen, Nare, Bakela, Nathan, Carl, Narraidoo, Nathalie, Nawaratna, Sujeevi, Ojo, Kayode K., Ortiz, Diana, Panic, Gordana, Papadatos, George, Parapini, Silvia, Patra, Kailash, Pham, Ngoc, Prats, Sarah, Plouffe, David M., Poulsen, Sally-Ann, Pradhan, Anupam, Quevedo, Celia, Quinn, Ronald J., Rice, Christopher A., Abdo Rizk, Mohamed, Ruecker, Andrea, St. Onge, Robert, Salgado Ferreira, Rafaela, Samra, Jasmeet, Robinett, Natalie G., Schlecht, Ulrich, Schmitt, Marjorie, Silva Villela, Filipe, Silvestrini, Francesco, Sinden, Robert, Smith, Dennis A., Soldati, Thierry, Spitzmüller, Andreas, Stamm, Serge Maximilian, Sullivan, David J., Sullivan, William, Suresh, Sundari, Suzuki, Brian M., Suzuki, Yo, Swamidass, S. Joshua, Taramelli, Donatella, Tchokouaha, Lauve R.Y., Theron, Anjo, Thomas, David, Tonissen, Kathryn F., Townson, Simon, Tripathi, Abhai K., Trofimov, Valentin, Udenze, Kenneth O., Ullah, Imran, Vallieres, Cindy, Vigil, Edgar, Vinetz, Joseph M., Voong Vinh, Phat, Vu, Hoan, Watanabe, Nao-aki, Weatherby, Kate, White, Pamela M., Wilks, Andrew F., Winzeler, Elizabeth A., Wojcik, Edward, Wree, Melanie, Wu, Wesley, Yokoyama, Naoaki, Zollo, Paul H. A., Abla, Nada, Blasco, Benjamin, Burrows, Jeremy, Laleu, Benoît, Leroy, Didier, Spangenberg, Thomas, Wells, Timothy, and Willis, Paul A.
- Abstract
A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemis
- Full Text
- View/download PDF
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