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5. Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets

Author

Knezevic, Claire E, Wright, Gabriela, Rix, Lily L Remsing, Kim, Woosuk, Kuenzi, Brent M, Luo, Yunting, Watters, January M, Koomen, John M, Haura, Eric B, Monteiro, Alvaro N, Radu, Caius, Lawrence, Harshani R, and Rix, Uwe

Subjects
Biochemistry and Cell Biology, Chemical Sciences, Biological Sciences, Orphan Drug, Biotechnology, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Cancer, Good Health and Well Being, H6PD, PARP inhibitor, chemical proteomics, polypharmacology, target identification, target selectivity, Biochemistry and cell biology, Medicinal and biomolecular chemistry
Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we generated a comparative proteome-wide target map of the four clinical PARPi, olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high target selectivity. However, in addition to the canonical targets PARP1, PARP2, and several of their binding partners, we also identified hexose-6-phosphate dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized targets of rucaparib and niraparib, respectively. Subsequent functional validation suggested that inhibition of DCK by niraparib could have detrimental effects when combined with nucleoside analog pro-drugs. H6PD silencing can cause apoptosis and further sensitize cells to PARPi, suggesting that H6PD may be, in addition to its established role in metabolic disorders, a new anticancer target.

Published
2016

13. Supplementary Table S1 from Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML

Author

Letson, Christopher T., primary, Balasis, Maria E., primary, Newman, Hannah, primary, Binder, Moritz, primary, Vedder, Alexis, primary, Kinose, Fumi, primary, Ball, Markus, primary, Kruer, Traci, primary, Quintana, Ariel, primary, Lasho, Terra L., primary, Finke, Christy M., primary, Almada, Luciana L., primary, Grants, Jennifer M., primary, Zhang, Guolin, primary, Fernandez-Zapico, Martin E., primary, Gaspar-Maia, Alexandre, primary, Lancet, Jeffrey, primary, Komrokji, Rami, primary, Haura, Eric, primary, Sallman, David A., primary, Reuther, Gary W., primary, Karsan, Aly, primary, Rix, Uwe, primary, Patnaik, Mrinal M., primary, and Padron, Eric, primary

Published
2023
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14. Supplementary Figure S2 from Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML

Author

Letson, Christopher T., primary, Balasis, Maria E., primary, Newman, Hannah, primary, Binder, Moritz, primary, Vedder, Alexis, primary, Kinose, Fumi, primary, Ball, Markus, primary, Kruer, Traci, primary, Quintana, Ariel, primary, Lasho, Terra L., primary, Finke, Christy M., primary, Almada, Luciana L., primary, Grants, Jennifer M., primary, Zhang, Guolin, primary, Fernandez-Zapico, Martin E., primary, Gaspar-Maia, Alexandre, primary, Lancet, Jeffrey, primary, Komrokji, Rami, primary, Haura, Eric, primary, Sallman, David A., primary, Reuther, Gary W., primary, Karsan, Aly, primary, Rix, Uwe, primary, Patnaik, Mrinal M., primary, and Padron, Eric, primary

Published
2023
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15. Supplementary Data S1 from Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML

Author

Letson, Christopher T., primary, Balasis, Maria E., primary, Newman, Hannah, primary, Binder, Moritz, primary, Vedder, Alexis, primary, Kinose, Fumi, primary, Ball, Markus, primary, Kruer, Traci, primary, Quintana, Ariel, primary, Lasho, Terra L., primary, Finke, Christy M., primary, Almada, Luciana L., primary, Grants, Jennifer M., primary, Zhang, Guolin, primary, Fernandez-Zapico, Martin E., primary, Gaspar-Maia, Alexandre, primary, Lancet, Jeffrey, primary, Komrokji, Rami, primary, Haura, Eric, primary, Sallman, David A., primary, Reuther, Gary W., primary, Karsan, Aly, primary, Rix, Uwe, primary, Patnaik, Mrinal M., primary, and Padron, Eric, primary

Published
2023
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16. Data from Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML

Author

Letson, Christopher T., primary, Balasis, Maria E., primary, Newman, Hannah, primary, Binder, Moritz, primary, Vedder, Alexis, primary, Kinose, Fumi, primary, Ball, Markus, primary, Kruer, Traci, primary, Quintana, Ariel, primary, Lasho, Terra L., primary, Finke, Christy M., primary, Almada, Luciana L., primary, Grants, Jennifer M., primary, Zhang, Guolin, primary, Fernandez-Zapico, Martin E., primary, Gaspar-Maia, Alexandre, primary, Lancet, Jeffrey, primary, Komrokji, Rami, primary, Haura, Eric, primary, Sallman, David A., primary, Reuther, Gary W., primary, Karsan, Aly, primary, Rix, Uwe, primary, Patnaik, Mrinal M., primary, and Padron, Eric, primary

Published
2023
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18. Targeting BET Proteins Downregulates miR-33a To Promote Synergy with PIM Inhibitors in CMML

Author

Letson, Christopher T., primary, Balasis, Maria E., additional, Newman, Hannah, additional, Binder, Moritz, additional, Vedder, Alexis, additional, Kinose, Fumi, additional, Ball, Markus, additional, Kruer, Traci, additional, Quintana, Ariel, additional, Lasho, Terra L., additional, Finke, Christy M., additional, Almada, Luciana L., additional, Grants, Jennifer M., additional, Zhang, Guolin, additional, Fernandez-Zapico, Martin E., additional, Gaspar-Maia, Alexandre, additional, Lancet, Jeffrey, additional, Komrokji, Rami, additional, Haura, Eric, additional, Sallman, David A., additional, Reuther, Gary W., additional, Karsan, Aly, additional, Rix, Uwe, additional, Patnaik, Mrinal M., additional, and Padron, Eric, additional

Published
2023
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19. Abstract B015: Wildtype RAS activity and PI3K signaling as new vulnerabilities in cells with acquired resistance to sotorasib

Author

Imbody, Denis, primary, Solanki, Hitendra S., additional, Desai, Bina, additional, Stewart, Paul A., additional, Stern, Yaakov, additional, Kato, Ryoji, additional, Majumder, Anurima, additional, Bridenstine, Liznair, additional, Xieraili, Aobuli, additional, Fang, Bin, additional, Darville, Lancia, additional, Kinose, Fumi, additional, Koomen, John M., additional, Rix, Uwe, additional, Marusyk, Andriy, additional, and Haura, Eric B., additional

Published
2023
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20. Data from Targeted Therapy Given after Anti–PD-1 Leads to Prolonged Responses in Mouse Melanoma Models through Sustained Antitumor Immunity

Author

Phadke, Manali S., primary, Chen, Zhihua, primary, Li, Jiannong, primary, Mohamed, Eslam, primary, Davies, Michael A., primary, Smalley, Inna, primary, Duckett, Derek R., primary, Palve, Vinayak, primary, Czerniecki, Brian J., primary, Forsyth, Peter A., primary, Noyes, David, primary, Adeegbe, Dennis O., primary, Eroglu, Zeynep, primary, Nguyen, Kimberly T., primary, Tsai, Kenneth Y., primary, Rix, Uwe, primary, Burd, Christin E., primary, Chen, Yian A., primary, Rodriguez, Paulo C., primary, and Smalley, Keiran S.M., primary

Published
2023
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22. Supplementary Figures and Table from Targeted Therapy Given after Anti–PD-1 Leads to Prolonged Responses in Mouse Melanoma Models through Sustained Antitumor Immunity

Author

Phadke, Manali S., primary, Chen, Zhihua, primary, Li, Jiannong, primary, Mohamed, Eslam, primary, Davies, Michael A., primary, Smalley, Inna, primary, Duckett, Derek R., primary, Palve, Vinayak, primary, Czerniecki, Brian J., primary, Forsyth, Peter A., primary, Noyes, David, primary, Adeegbe, Dennis O., primary, Eroglu, Zeynep, primary, Nguyen, Kimberly T., primary, Tsai, Kenneth Y., primary, Rix, Uwe, primary, Burd, Christin E., primary, Chen, Yian A., primary, Rodriguez, Paulo C., primary, and Smalley, Keiran S.M., primary

Published
2023
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24. Data from Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer

Author

Nerlakanti, Niveditha, primary, Yao, Jiqiang, primary, Nguyen, Duy T., primary, Patel, Ami K., primary, Eroshkin, Alexey M., primary, Lawrence, Harshani R., primary, Ayaz, Muhammad, primary, Kuenzi, Brent M., primary, Agarwal, Neha, primary, Chen, Yunyun, primary, Gunawan, Steven, primary, Karim, Rezaul M., primary, Berndt, Norbert, primary, Puskas, John, primary, Magliocco, Anthony M., primary, Coppola, Domenico, primary, Dhillon, Jasreman, primary, Zhang, Jingsong, primary, Shymalagovindarajan, Subramaniam, primary, Rix, Uwe, primary, Kim, Youngchul, primary, Perera, Ranjan, primary, Lawrence, Nicholas J., primary, Schonbrunn, Ernst, primary, and Mahajan, Kiran, primary

Published
2023
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25. Supplementary Figure S6 from PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer

Author

Jhuraney, Ankita, primary, Woods, Nicholas T., primary, Wright, Gabriela, primary, Rix, Lily, primary, Kinose, Fumi, primary, Kroeger, Jodi L., primary, Remily-Wood, Elizabeth, primary, Cress, W. Douglas, primary, Koomen, John M., primary, Brantley, Stephen G., primary, Gray, Jhanelle E., primary, Haura, Eric B., primary, Rix, Uwe, primary, and Monteiro, Alvaro N., primary

Published
2023
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29. Data from TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors

Author

Cocco, Emiliano, primary, Lee, Ji Eun, primary, Kannan, Srinivasaraghavan, primary, Schram, Alison M., primary, Won, Helen H., primary, Shifman, Sophie, primary, Kulick, Amanda, primary, Baldino, Laura, primary, Toska, Eneda, primary, Arruabarrena-Aristorena, Amaia, primary, Kittane, Srushti, primary, Wu, Fan, primary, Cai, Yanyan, primary, Arena, Sabrina, primary, Mussolin, Benedetta, primary, Kannan, Ram, primary, Vasan, Neil, primary, Gorelick, Alexander N., primary, Berger, Michael F., primary, Novoplansky, Ofra, primary, Jagadeeshan, Sankar, primary, Liao, Yi, primary, Rix, Uwe, primary, Misale, Sandra, primary, Taylor, Barry S., primary, Bardelli, Alberto, primary, Hechtman, Jaclyn F., primary, Hyman, David M., primary, Elkabets, Moshe, primary, de Stanchina, Elisa, primary, Verma, Chandra S., primary, Ventura, Andrea, primary, Drilon, Alexander, primary, and Scaltriti, Maurizio, primary

Published
2023
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31. Supplementary Table S2 from PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer

Author

Jhuraney, Ankita, primary, Woods, Nicholas T., primary, Wright, Gabriela, primary, Rix, Lily, primary, Kinose, Fumi, primary, Kroeger, Jodi L., primary, Remily-Wood, Elizabeth, primary, Cress, W. Douglas, primary, Koomen, John M., primary, Brantley, Stephen G., primary, Gray, Jhanelle E., primary, Haura, Eric B., primary, Rix, Uwe, primary, and Monteiro, Alvaro N., primary

Published
2023
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32. Supplementary Figure Legends 1-5, Table Legends 1-5 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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35. Supplementary Figures S1-S7 and Supplementary Methods from Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer

Author

Nerlakanti, Niveditha, primary, Yao, Jiqiang, primary, Nguyen, Duy T., primary, Patel, Ami K., primary, Eroshkin, Alexey M., primary, Lawrence, Harshani R., primary, Ayaz, Muhammad, primary, Kuenzi, Brent M., primary, Agarwal, Neha, primary, Chen, Yunyun, primary, Gunawan, Steven, primary, Karim, Rezaul M., primary, Berndt, Norbert, primary, Puskas, John, primary, Magliocco, Anthony M., primary, Coppola, Domenico, primary, Dhillon, Jasreman, primary, Zhang, Jingsong, primary, Shymalagovindarajan, Subramaniam, primary, Rix, Uwe, primary, Kim, Youngchul, primary, Perera, Ranjan, primary, Lawrence, Nicholas J., primary, Schonbrunn, Ernst, primary, and Mahajan, Kiran, primary

Published
2023
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36. Data from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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37. Data from PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer

Author

Jhuraney, Ankita, primary, Woods, Nicholas T., primary, Wright, Gabriela, primary, Rix, Lily, primary, Kinose, Fumi, primary, Kroeger, Jodi L., primary, Remily-Wood, Elizabeth, primary, Cress, W. Douglas, primary, Koomen, John M., primary, Brantley, Stephen G., primary, Gray, Jhanelle E., primary, Haura, Eric B., primary, Rix, Uwe, primary, and Monteiro, Alvaro N., primary

Published
2023
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38. Supplementary Tables S1 to S10 from Targeting the BRD4-HOXB13 Coregulated Transcriptional Networks with Bromodomain-Kinase Inhibitors to Suppress Metastatic Castration-Resistant Prostate Cancer

Author

Nerlakanti, Niveditha, primary, Yao, Jiqiang, primary, Nguyen, Duy T., primary, Patel, Ami K., primary, Eroshkin, Alexey M., primary, Lawrence, Harshani R., primary, Ayaz, Muhammad, primary, Kuenzi, Brent M., primary, Agarwal, Neha, primary, Chen, Yunyun, primary, Gunawan, Steven, primary, Karim, Rezaul M., primary, Berndt, Norbert, primary, Puskas, John, primary, Magliocco, Anthony M., primary, Coppola, Domenico, primary, Dhillon, Jasreman, primary, Zhang, Jingsong, primary, Shymalagovindarajan, Subramaniam, primary, Rix, Uwe, primary, Kim, Youngchul, primary, Perera, Ranjan, primary, Lawrence, Nicholas J., primary, Schonbrunn, Ernst, primary, and Mahajan, Kiran, primary

Published
2023
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39. Supplementary Materials and Methods from PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer

Author

Jhuraney, Ankita, primary, Woods, Nicholas T., primary, Wright, Gabriela, primary, Rix, Lily, primary, Kinose, Fumi, primary, Kroeger, Jodi L., primary, Remily-Wood, Elizabeth, primary, Cress, W. Douglas, primary, Koomen, John M., primary, Brantley, Stephen G., primary, Gray, Jhanelle E., primary, Haura, Eric B., primary, Rix, Uwe, primary, and Monteiro, Alvaro N., primary

Published
2023
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43. Supplementary Table 1 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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44. Supp Materials legends from PAXIP1 Potentiates the Combination of WEE1 Inhibitor AZD1775 and Platinum Agents in Lung Cancer

Author

Jhuraney, Ankita, primary, Woods, Nicholas T., primary, Wright, Gabriela, primary, Rix, Lily, primary, Kinose, Fumi, primary, Kroeger, Jodi L., primary, Remily-Wood, Elizabeth, primary, Cress, W. Douglas, primary, Koomen, John M., primary, Brantley, Stephen G., primary, Gray, Jhanelle E., primary, Haura, Eric B., primary, Rix, Uwe, primary, and Monteiro, Alvaro N., primary

Published
2023
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45. Supplementary Figures from TRK xDFG Mutations Trigger a Sensitivity Switch from Type I to II Kinase Inhibitors

Author

Cocco, Emiliano, primary, Lee, Ji Eun, primary, Kannan, Srinivasaraghavan, primary, Schram, Alison M., primary, Won, Helen H., primary, Shifman, Sophie, primary, Kulick, Amanda, primary, Baldino, Laura, primary, Toska, Eneda, primary, Arruabarrena-Aristorena, Amaia, primary, Kittane, Srushti, primary, Wu, Fan, primary, Cai, Yanyan, primary, Arena, Sabrina, primary, Mussolin, Benedetta, primary, Kannan, Ram, primary, Vasan, Neil, primary, Gorelick, Alexander N., primary, Berger, Michael F., primary, Novoplansky, Ofra, primary, Jagadeeshan, Sankar, primary, Liao, Yi, primary, Rix, Uwe, primary, Misale, Sandra, primary, Taylor, Barry S., primary, Bardelli, Alberto, primary, Hechtman, Jaclyn F., primary, Hyman, David M., primary, Elkabets, Moshe, primary, de Stanchina, Elisa, primary, Verma, Chandra S., primary, Ventura, Andrea, primary, Drilon, Alexander, primary, and Scaltriti, Maurizio, primary

Published
2023
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47. Supplementary Figure 5 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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48. Supplementary Table 4 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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49. Supplementary Table 3 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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50. Supplementary Table 2 from An Integrated Chemical Biology Approach Identifies Specific Vulnerability of Ewing's Sarcoma to Combined Inhibition of Aurora Kinases A and B

Author

Winter, Georg E., primary, Rix, Uwe, primary, Lissat, Andrej, primary, Stukalov, Alexey, primary, Müllner, Markus K., primary, Bennett, Keiryn L., primary, Colinge, Jacques, primary, Nijman, Sebastian M., primary, Kubicek, Stefan, primary, Kovar, Heinrich, primary, Kontny, Udo, primary, and Superti-Furga, Giulio, primary

Published
2023
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