Search

Your search keyword '"Silva, Arthur C"' showing total 18 results
Start Over Author "Silva, Arthur C"
18 results on '"Silva, Arthur C"'

3. Shortcuts to schistosomiasis drug discovery: The state-of-the-art

Author

Moreira-Filho, José T., primary, Dantas, Rafael F., additional, Senger, Mário R., additional, Silva, Arthur C., additional, Campos, Dulcinea M.B., additional, Muratov, Eugene, additional, Silva-Junior, Floriano P., additional, Andrade, Carolina H., additional, and Neves, Bruno J., additional

Published
2019
Full Text
View/download PDF

4. STopTox: An in Silico Alternative to Animal Testing for Acute Systemic and Topical Toxicity

Author

Borba, Joyce V.B., primary, Alves, Vinicius M., additional, Braga, Rodolpho C., additional, Korn, Daniel R., additional, Overdahl, Kirsten, additional, Silva, Arthur C., additional, Hall, Steven U.S., additional, Overdahl, Erik, additional, Kleinstreuer, Nicole, additional, Strickland, Judy, additional, Allen, David, additional, Andrade, Carolina Horta, additional, Muratov, Eugene N., additional, and Tropsha, Alexander, additional

Published
2022
Full Text
View/download PDF

5. Erratum: CATMoS: Collaborative Acute Toxicity Modeling Suite

Author

Mansouri, Kamel, primary, Karmaus, Agnes L., additional, Fitzpatrick, Jeremy, additional, Patlewicz, Grace, additional, Pradeep, Prachi, additional, Alberga, Domenico, additional, Alepee, Nathalie, additional, Allen, Timothy E.H., additional, Allen, Dave, additional, Alves, Vinicius M., additional, Andrade, Carolina H., additional, Auernhammer, Tyler R., additional, Ballabio, Davide, additional, Bell, Shannon, additional, Benfenati, Emilio, additional, Bhattacharya, Sudin, additional, Bastos, Joyce V., additional, Boyd, Stephen, additional, Brown, J. B., additional, Capuzzi, Stephen J., additional, Chushak, Yaroslav, additional, Ciallella, Heather, additional, Clark, Alex M., additional, Consonni, Viviana, additional, Daga, Pankaj R., additional, Ekins, Sean, additional, Farag, Sherif, additional, Fedorov, Maxim, additional, Fourches, Denis, additional, Gadaleta, Domenico, additional, Gao, Feng, additional, Gearhart, Jeffery M., additional, Goh, Garett, additional, Goodman, Jonathan M., additional, Grisoni, Francesca, additional, Grulke, Christopher M., additional, Hartung, Thomas, additional, Hirn, Matthew, additional, Karpov, Pavel, additional, Korotcov, Alexandru, additional, Lavado, Giovanna J., additional, Lawless, Michael, additional, Li, Xinhao, additional, Luechtefeld, Thomas, additional, Lunghini, Filippo, additional, Mangiatordi, Giuseppe F., additional, Marcou, Gilles, additional, Marsh, Dan, additional, Martin, Todd, additional, Mauri, Andrea, additional, Muratov, Eugene N., additional, Myatt, Glenn J., additional, Nguyen, Dac-Trung, additional, Nicolotti, Orazio, additional, Note, Reine, additional, Pande, Paritosh, additional, Parks, Amanda K., additional, Peryea, Tyler, additional, Polash, Ahsan H., additional, Rallo, Robert, additional, Roncaglioni, Alessandra, additional, Rowlands, Craig, additional, Ruiz, Patricia, additional, Russo, Daniel P., additional, Sayed, Ahmed, additional, Sayre, Risa, additional, Sheils, Timothy, additional, Siegel, Charles, additional, Silva, Arthur C., additional, Simeonov, Anton, additional, Sosnin, Sergey, additional, Southall, Noel, additional, Strickland, Judy, additional, Tang, Yun, additional, Teppen, Brian, additional, Tetko, Igor V., additional, Thomas, Dennis, additional, Tkachenko, Valery, additional, Todeschini, Roberto, additional, Toma, Cosimo, additional, Tripodi, Ignacio, additional, Trisciuzzi, Daniela, additional, Tropsha, Alexander, additional, Varnek, Alexandre, additional, Vukovic, Kristijan, additional, Wang, Zhongyu, additional, Wang, Liguo, additional, Waters, Katrina M., additional, Wedlake, Andrew J., additional, Wijeyesakere, Sanjeeva J., additional, Wilson, Dan, additional, Xiao, Zijun, additional, Yang, Hongbin, additional, Zahoranszky-Kohalmi, Gergely, additional, Zakharov, Alexey V., additional, Zhang, Fagen F., additional, Zhang, Zhen, additional, Zhao, Tongan, additional, Zhu, Hao, additional, Zorn, Kimberley M., additional, Casey, Warren, additional, and Kleinstreuer, Nicole C., additional

Published
2021
Full Text
View/download PDF

6. Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence

Author

Moreira-Filho, José T, Silva, Arthur C, Dantas, Rafael F, Gomes, Barbara F, Souza Neto, Lauro R, Brandao-Neto, Jose, Owens, Raymond J, Furnham, Nicholas, Neves, Bruno J, Silva-Junior, Floriano P, and Andrade, Carolina H

Subjects
parasitic diseases
Abstract

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor.

Published
2021

7. CATMoS: Collaborative Acute Toxicity Modeling Suite

Author

Mansouri, K, Karmaus, A, Fitzpatrick, J, Patlewicz, G, Pradeep, P, Alberga, D, Alepee, N, Allen, T, Allen, D, Alves, V, Andrade, C, Auernhammer, T, Ballabio, D, Bell, S, Benfenati, E, Bhattacharya, S, Bastos, J, Boyd, S, Brown, J, Capuzzi, S, Chushak, Y, Ciallella, H, Clark, A, Consonni, V, Daga, P, Ekins, S, Farag, S, Fedorov, M, Fourches, D, Gadaleta, D, Gao, F, Gearhart, J, Goh, G, Goodman, J, Grisoni, F, Grulke, C, Hartung, T, Hirn, M, Karpov, P, Korotcov, A, Lavado, G, Lawless, M, Li, X, Luechtefeld, T, Lunghini, F, Mangiatordi, G, Marcou, G, Marsh, D, Martin, T, Mauri, A, Muratov, E, Myatt, G, Nguyen, D, Nicolotti, O, Note, R, Pande, P, Parks, A, Peryea, T, Polash, A, Rallo, R, Roncaglioni, A, Rowlands, C, Ruiz, P, Russo, D, Sayed, A, Sayre, R, Sheils, T, Siegel, C, Silva, A, Simeonov, A, Sosnin, S, Southall, N, Strickland, J, Tang, Y, Teppen, B, Tetko, I, Thomas, D, Tkachenko, V, Todeschini, R, Toma, C, Tripodi, I, Trisciuzzi, D, Tropsha, A, Varnek, A, Vukovic, K, Wang, Z, Wang, L, Waters, K, Wedlake, A, Wijeyesakere, S, Wilson, D, Xiao, Z, Yang, H, Zahoranszky-Kohalmi, G, Zakharov, A, Zhang, F, Zhang, Z, Zhao, T, Zhu, H, Zorn, K, Casey, W, Kleinstreuer, N, Mansouri, Kamel, Karmaus, Agnes L, Fitzpatrick, Jeremy, Patlewicz, Grace, Pradeep, Prachi, Alberga, Domenico, Alepee, Nathalie, Allen, Timothy E H, Allen, Dave, Alves, Vinicius M, Andrade, Carolina H, Auernhammer, Tyler R, Ballabio, Davide, Bell, Shannon, Benfenati, Emilio, Bhattacharya, Sudin, Bastos, Joyce V, Boyd, Stephen, Brown, J B, Capuzzi, Stephen J, Chushak, Yaroslav, Ciallella, Heather, Clark, Alex M, Consonni, Viviana, Daga, Pankaj R, Ekins, Sean, Farag, Sherif, Fedorov, Maxim, Fourches, Denis, Gadaleta, Domenico, Gao, Feng, Gearhart, Jeffery M, Goh, Garett, Goodman, Jonathan M, Grisoni, Francesca, Grulke, Christopher M, Hartung, Thomas, Hirn, Matthew, Karpov, Pavel, Korotcov, Alexandru, Lavado, Giovanna J, Lawless, Michael, Li, Xinhao, Luechtefeld, Thomas, Lunghini, Filippo, Mangiatordi, Giuseppe F, Marcou, Gilles, Marsh, Dan, Martin, Todd, Mauri, Andrea, Muratov, Eugene N, Myatt, Glenn J, Nguyen, Dac-Trung, Nicolotti, Orazio, Note, Reine, Pande, Paritosh, Parks, Amanda K, Peryea, Tyler, Polash, Ahsan H, Rallo, Robert, Roncaglioni, Alessandra, Rowlands, Craig, Ruiz, Patricia, Russo, Daniel P, Sayed, Ahmed, Sayre, Risa, Sheils, Timothy, Siegel, Charles, Silva, Arthur C, Simeonov, Anton, Sosnin, Sergey, Southall, Noel, Strickland, Judy, Tang, Yun, Teppen, Brian, Tetko, Igor V, Thomas, Dennis, Tkachenko, Valery, Todeschini, Roberto, Toma, Cosimo, Tripodi, Ignacio, Trisciuzzi, Daniela, Tropsha, Alexander, Varnek, Alexandre, Vukovic, Kristijan, Wang, Zhongyu, Wang, Liguo, Waters, Katrina M, Wedlake, Andrew J, Wijeyesakere, Sanjeeva J, Wilson, Dan, Xiao, Zijun, Yang, Hongbin, Zahoranszky-Kohalmi, Gergely, Zakharov, Alexey V, Zhang, Fagen F, Zhang, Zhen, Zhao, Tongan, Zhu, Hao, Zorn, Kimberley M, Casey, Warren, Kleinstreuer, Nicole C, Mansouri, K, Karmaus, A, Fitzpatrick, J, Patlewicz, G, Pradeep, P, Alberga, D, Alepee, N, Allen, T, Allen, D, Alves, V, Andrade, C, Auernhammer, T, Ballabio, D, Bell, S, Benfenati, E, Bhattacharya, S, Bastos, J, Boyd, S, Brown, J, Capuzzi, S, Chushak, Y, Ciallella, H, Clark, A, Consonni, V, Daga, P, Ekins, S, Farag, S, Fedorov, M, Fourches, D, Gadaleta, D, Gao, F, Gearhart, J, Goh, G, Goodman, J, Grisoni, F, Grulke, C, Hartung, T, Hirn, M, Karpov, P, Korotcov, A, Lavado, G, Lawless, M, Li, X, Luechtefeld, T, Lunghini, F, Mangiatordi, G, Marcou, G, Marsh, D, Martin, T, Mauri, A, Muratov, E, Myatt, G, Nguyen, D, Nicolotti, O, Note, R, Pande, P, Parks, A, Peryea, T, Polash, A, Rallo, R, Roncaglioni, A, Rowlands, C, Ruiz, P, Russo, D, Sayed, A, Sayre, R, Sheils, T, Siegel, C, Silva, A, Simeonov, A, Sosnin, S, Southall, N, Strickland, J, Tang, Y, Teppen, B, Tetko, I, Thomas, D, Tkachenko, V, Todeschini, R, Toma, C, Tripodi, I, Trisciuzzi, D, Tropsha, A, Varnek, A, Vukovic, K, Wang, Z, Wang, L, Waters, K, Wedlake, A, Wijeyesakere, S, Wilson, D, Xiao, Z, Yang, H, Zahoranszky-Kohalmi, G, Zakharov, A, Zhang, F, Zhang, Z, Zhao, T, Zhu, H, Zorn, K, Casey, W, Kleinstreuer, N, Mansouri, Kamel, Karmaus, Agnes L, Fitzpatrick, Jeremy, Patlewicz, Grace, Pradeep, Prachi, Alberga, Domenico, Alepee, Nathalie, Allen, Timothy E H, Allen, Dave, Alves, Vinicius M, Andrade, Carolina H, Auernhammer, Tyler R, Ballabio, Davide, Bell, Shannon, Benfenati, Emilio, Bhattacharya, Sudin, Bastos, Joyce V, Boyd, Stephen, Brown, J B, Capuzzi, Stephen J, Chushak, Yaroslav, Ciallella, Heather, Clark, Alex M, Consonni, Viviana, Daga, Pankaj R, Ekins, Sean, Farag, Sherif, Fedorov, Maxim, Fourches, Denis, Gadaleta, Domenico, Gao, Feng, Gearhart, Jeffery M, Goh, Garett, Goodman, Jonathan M, Grisoni, Francesca, Grulke, Christopher M, Hartung, Thomas, Hirn, Matthew, Karpov, Pavel, Korotcov, Alexandru, Lavado, Giovanna J, Lawless, Michael, Li, Xinhao, Luechtefeld, Thomas, Lunghini, Filippo, Mangiatordi, Giuseppe F, Marcou, Gilles, Marsh, Dan, Martin, Todd, Mauri, Andrea, Muratov, Eugene N, Myatt, Glenn J, Nguyen, Dac-Trung, Nicolotti, Orazio, Note, Reine, Pande, Paritosh, Parks, Amanda K, Peryea, Tyler, Polash, Ahsan H, Rallo, Robert, Roncaglioni, Alessandra, Rowlands, Craig, Ruiz, Patricia, Russo, Daniel P, Sayed, Ahmed, Sayre, Risa, Sheils, Timothy, Siegel, Charles, Silva, Arthur C, Simeonov, Anton, Sosnin, Sergey, Southall, Noel, Strickland, Judy, Tang, Yun, Teppen, Brian, Tetko, Igor V, Thomas, Dennis, Tkachenko, Valery, Todeschini, Roberto, Toma, Cosimo, Tripodi, Ignacio, Trisciuzzi, Daniela, Tropsha, Alexander, Varnek, Alexandre, Vukovic, Kristijan, Wang, Zhongyu, Wang, Liguo, Waters, Katrina M, Wedlake, Andrew J, Wijeyesakere, Sanjeeva J, Wilson, Dan, Xiao, Zijun, Yang, Hongbin, Zahoranszky-Kohalmi, Gergely, Zakharov, Alexey V, Zhang, Fagen F, Zhang, Zhen, Zhao, Tongan, Zhu, Hao, Zorn, Kimberley M, Casey, Warren, and Kleinstreuer, Nicole C

Abstract

Background: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silica models built using existing data facilitate rapid acute tox- icity predictions without using animals. Objkctivks: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organ- ized an international collaboration to develop in silica models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). Mkthods: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. Results: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in viva results. Discussion: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in viva rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemica

Published
2021

8. CATMoS: Collaborative Acute Toxicity Modeling Suite

Author

Mansouri, Kamel, primary, Karmaus, Agnes L., additional, Fitzpatrick, Jeremy, additional, Patlewicz, Grace, additional, Pradeep, Prachi, additional, Alberga, Domenico, additional, Alepee, Nathalie, additional, Allen, Timothy E.H., additional, Allen, Dave, additional, Alves, Vinicius M., additional, Andrade, Carolina H., additional, Auernhammer, Tyler R., additional, Ballabio, Davide, additional, Bell, Shannon, additional, Benfenati, Emilio, additional, Bhattacharya, Sudin, additional, Bastos, Joyce V., additional, Boyd, Stephen, additional, Brown, J.B., additional, Capuzzi, Stephen J., additional, Chushak, Yaroslav, additional, Ciallella, Heather, additional, Clark, Alex M., additional, Consonni, Viviana, additional, Daga, Pankaj R., additional, Ekins, Sean, additional, Farag, Sherif, additional, Fedorov, Maxim, additional, Fourches, Denis, additional, Gadaleta, Domenico, additional, Gao, Feng, additional, Gearhart, Jeffery M., additional, Goh, Garett, additional, Goodman, Jonathan M., additional, Grisoni, Francesca, additional, Grulke, Christopher M., additional, Hartung, Thomas, additional, Hirn, Matthew, additional, Karpov, Pavel, additional, Korotcov, Alexandru, additional, Lavado, Giovanna J., additional, Lawless, Michael, additional, Li, Xinhao, additional, Luechtefeld, Thomas, additional, Lunghini, Filippo, additional, Mangiatordi, Giuseppe F., additional, Marcou, Gilles, additional, Marsh, Dan, additional, Martin, Todd, additional, Mauri, Andrea, additional, Muratov, Eugene N., additional, Myatt, Glenn J., additional, Nguyen, Dac-Trung, additional, Nicolotti, Orazio, additional, Note, Reine, additional, Pande, Paritosh, additional, Parks, Amanda K., additional, Peryea, Tyler, additional, Polash, Ahsan H., additional, Rallo, Robert, additional, Roncaglioni, Alessandra, additional, Rowlands, Craig, additional, Ruiz, Patricia, additional, Russo, Daniel P., additional, Sayed, Ahmed, additional, Sayre, Risa, additional, Sheils, Timothy, additional, Siegel, Charles, additional, Silva, Arthur C., additional, Simeonov, Anton, additional, Sosnin, Sergey, additional, Southall, Noel, additional, Strickland, Judy, additional, Tang, Yun, additional, Teppen, Brian, additional, Tetko, Igor V., additional, Thomas, Dennis, additional, Tkachenko, Valery, additional, Todeschini, Roberto, additional, Toma, Cosimo, additional, Tripodi, Ignacio, additional, Trisciuzzi, Daniela, additional, Tropsha, Alexander, additional, Varnek, Alexandre, additional, Vukovic, Kristijan, additional, Wang, Zhongyu, additional, Wang, Liguo, additional, Waters, Katrina M., additional, Wedlake, Andrew J., additional, Wijeyesakere, Sanjeeva J., additional, Wilson, Dan, additional, Xiao, Zijun, additional, Yang, Hongbin, additional, Zahoranszky-Kohalmi, Gergely, additional, Zakharov, Alexey V., additional, Zhang, Fagen F., additional, Zhang, Zhen, additional, Zhao, Tongan, additional, Zhu, Hao, additional, Zorn, Kimberley M., additional, Casey, Warren, additional, and Kleinstreuer, Nicole C., additional

Published
2021
Full Text
View/download PDF

9. Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual‐Stage Activity

Author

Lima, Marilia N. N., primary, Borba, Joyce V. B., additional, Cassiano, Gustavo C., additional, Mottin, Melina, additional, Mendonça, Sabrina S., additional, Silva, Arthur C., additional, Tomaz, Kaira C. P., additional, Calit, Juliana, additional, Bargieri, Daniel Y., additional, Costa, Fabio T. M., additional, and Andrade, Carolina H., additional

Published
2021
Full Text
View/download PDF

10. STopTox: An In-Silico Alternative to Animal Testing for Acute Systemic and TOPical TOXicity

Author

Borba, Joyce V. V. B., primary, Alves, Vinicius, primary, Braga, Rodolpho, primary, Korn, Daniel, primary, Overdahl, Kirsten, primary, Silva, Arthur C., primary, Hall, Steven, primary, Overdahl, Erik, primary, Strickland, Judy, primary, Allen, DAvid, primary, Kleinstreuer, Nicole, primary, Andrade, Carolina, primary, Muratov, Eugene, primary, and Tropsha, Alexander, primary

Published
2020
Full Text
View/download PDF

13. Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits

Author

Lima, Marilia N. N., primary, Cassiano, Gustavo C., additional, Tomaz, Kaira C. P., additional, Silva, Arthur C., additional, Sousa, Bruna K. P., additional, Ferreira, Leticia T., additional, Tavella, Tatyana A., additional, Calit, Juliana, additional, Bargieri, Daniel Y., additional, Neves, Bruno J., additional, Costa, Fabio T. M., additional, and Andrade, Carolina Horta, additional

Published
2019
Full Text
View/download PDF

16. CATMoS: Collaborative Acute Toxicity Modeling Suite

Author

Mansouri, Kamel, Karmaus, Agnes L, Fitzpatrick, Jeremy, Patlewicz, Grace, Pradeep, Prachi, Alberga, Domenico, Alepee, Nathalie, Allen, Timothy EH, Allen, Dave, Alves, Vinicius M, Andrade, Carolina H, Auernhammer, Tyler R, Ballabio, Davide, Bell, Shannon, Benfenati, Emilio, Bhattacharya, Sudin, Bastos, Joyce V, Boyd, Stephen, Brown, JB, Capuzzi, Stephen J, Chushak, Yaroslav, Ciallella, Heather, Clark, Alex M, Consonni, Viviana, Daga, Pankaj R, Ekins, Sean, Farag, Sherif, Fedorov, Maxim, Fourches, Denis, Gadaleta, Domenico, Gao, Feng, Gearhart, Jeffery M, Goh, Garett, Goodman, Jonathan M, Grisoni, Francesca, Grulke, Christopher M, Hartung, Thomas, Hirn, Matthew, Karpov, Pavel, Korotcov, Alexandru, Lavado, Giovanna J, Lawless, Michael, Li, Xinhao, Luechtefeld, Thomas, Lunghini, Filippo, Mangiatordi, Giuseppe F, Marcou, Gilles, Marsh, Dan, Martin, Todd, Mauri, Andrea, Muratov, Eugene N, Myatt, Glenn J, Nguyen, Dac-Trung, Nicolotti, Orazio, Note, Reine, Pande, Paritosh, Parks, Amanda K, Peryea, Tyler, Polash, Ahsan H, Rallo, Robert, Roncaglioni, Alessandra, Rowlands, Craig, Ruiz, Patricia, Russo, Daniel P, Sayed, Ahmed, Sayre, Risa, Sheils, Timothy, Siegel, Charles, Silva, Arthur C, Simeonov, Anton, Sosnin, Sergey, Southall, Noel, Strickland, Judy, Tang, Yun, Teppen, Brian, Tetko, Igor V, Thomas, Dennis, Tkachenko, Valery, Todeschini, Roberto, Toma, Cosimo, Tripodi, Ignacio, Trisciuzzi, Daniela, Tropsha, Alexander, Varnek, Alexandre, Vukovic, Kristijan, Wang, Zhongyu, Wang, Liguo, Waters, Katrina M, Wedlake, Andrew J, Wijeyesakere, Sanjeeva J, Wilson, Dan, Xiao, Zijun, Yang, Hongbin, Zahoranszky-Kohalmi, Gergely, Zakharov, Alexey V, Zhang, Fagen F, Zhang, Zhen, Zhao, Tongan, Zhu, Hao, Zorn, Kimberley M, Casey, Warren, and Kleinstreuer, Nicole C

Subjects
Government Agencies, 13. Climate action, Toxicity Tests, Acute, Animals, Computer Simulation, United States Environmental Protection Agency, United States, 3. Good health, Rats
Abstract

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. In silico models built using existing data facilitate rapid acute toxicity predictions without using animals. OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop in silico models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50≤50mg/kg)], and nontoxic chemicals (LD50>2,000mg/kg). METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches. RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495.

17. Schistosomiasis Drug Discovery in the Era of Automation and Artificial Intelligence.

Author

Moreira-Filho JT, Silva AC, Dantas RF, Gomes BF, Souza Neto LR, Brandao-Neto J, Owens RJ, Furnham N, Neves BJ, Silva-Junior FP, and Andrade CH

Subjects
Animals, Humans, Artificial Intelligence, Drug Discovery methods, Schistosoma drug effects, Schistosomiasis drug therapy, Schistosomicides
Abstract

Schistosomiasis is a parasitic disease caused by trematode worms of the genus Schistosoma and affects over 200 million people worldwide. The control and treatment of this neglected tropical disease is based on a single drug, praziquantel, which raises concerns about the development of drug resistance. This, and the lack of efficacy of praziquantel against juvenile worms, highlights the urgency for new antischistosomal therapies. In this review we focus on innovative approaches to the identification of antischistosomal drug candidates, including the use of automated assays, fragment-based screening, computer-aided and artificial intelligence-based computational methods. We highlight the current developments that may contribute to optimizing research outputs and lead to more effective drugs for this highly prevalent disease, in a more cost-effective drug discovery endeavor., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer CC declared a past co-authorship with one of the authors CA to the handling Editor., (Copyright © 2021 Moreira-Filho, Silva, Dantas, Gomes, Souza Neto, Brandao-Neto, Owens, Furnham, Neves, Silva-Junior and Andrade.)

Published
2021
Full Text
View/download PDF

18. Virtual screening strategies in medicinal chemistry: the state of the art and current challenges.

Author

Braga RC, Alves VM, Silva AC, Nascimento MN, Silva FC, Liao LM, and Andrade CH

Subjects
14-alpha Demethylase Inhibitors chemical synthesis, 14-alpha Demethylase Inhibitors chemistry, Animals, Chemistry, Pharmaceutical, Humans, Trypanosoma cruzi enzymology, 14-alpha Demethylase Inhibitors pharmacology, Drug Evaluation, Preclinical, Sterol 14-Demethylase metabolism
Abstract

Virtual screening (VS) techniques are well-established tools in the modern drug discovery process, mainly used for hit finding in drug discovery. The availability of knowledge of structural information, which includes an increasing number of 3D protein structures and the readiness of free databases of commercially available smallmolecules, provides a broad platform for VS. This review summarizes the current developments in VS regarding chemical databases and highlights the achievements as well as the challenges with an emphasis on a recent example of the successful application for the identification of new hits for sterol 14α-demethylase (CYP51) of Trypanosoma cruzi.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results