Search

Your search keyword '"Guo Zhu Zheng"' showing total 12 results
Start Over Author "Guo Zhu Zheng" Publisher american association for cancer research (aacr)
12 results on '"Guo Zhu Zheng"'

1. Figures S20-S23 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

H3B-5942 in combination with palbocyclib shows synergy in vitro and in vivo

Published
2023
Full Text
View/download PDF

2. Supplementary Methods from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

Additional methods provided.

Published
2023
Full Text
View/download PDF

3. Figures S13-S19 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

H3B-5942 exhibits dose-dependent inhibition of ER target genes and shows significant efficacy ER Wt and mutant in vivo models

Published
2023
Full Text
View/download PDF

4. Figures S11-S12 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

H3B-5942 suppresses co-activator recruitment and shows potency in endocrine sensitive and resistant lines

Published
2023
Full Text
View/download PDF

5. Figures S1-S6 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

ESR1 mutants are resistant to endocrine therapies in vitro and in vivo and H3B-5942 can suppress ER pathway activity.

Published
2023
Full Text
View/download PDF

6. Supplementary Figure from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer

Author

Manav Korpal, Ping Zhu, Sudeep Prajapati, Guo Zhu Zheng, Nicholas Larsen, David M. Bolduc, Frédéric H. Vaillancourt, Hao Zeng, Xun Zhang, Shihua Yao, Michael J. Wick, Tarek Sahmoud, Victoria Rimkunas, Tuong-Vi Nguyen, Karthikeyan Murugesan, Alyssa D. Moriarty, Meagan Montesion, Amy Kim, Sean Irwin, Ming-Hong Hao, Lee A. Albacker, Kiran B. Aithal, Deepti Banka, Zhenhua J. Wu, Zhaojie Zhang, Xiaoling Puyang, and Craig Furman

Abstract

Supplementary Figure from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer

Published
2023
Full Text
View/download PDF

7. Figures S7-S10 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

C530 residue is critical for H3B-5942 potency

Published
2023
Full Text
View/download PDF

8. Supplementary Data from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer

Author

Manav Korpal, Ping Zhu, Sudeep Prajapati, Guo Zhu Zheng, Nicholas Larsen, David M. Bolduc, Frédéric H. Vaillancourt, Hao Zeng, Xun Zhang, Shihua Yao, Michael J. Wick, Tarek Sahmoud, Victoria Rimkunas, Tuong-Vi Nguyen, Karthikeyan Murugesan, Alyssa D. Moriarty, Meagan Montesion, Amy Kim, Sean Irwin, Ming-Hong Hao, Lee A. Albacker, Kiran B. Aithal, Deepti Banka, Zhenhua J. Wu, Zhaojie Zhang, Xiaoling Puyang, and Craig Furman

Abstract

Supplementary Data from Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer

Published
2023
Full Text
View/download PDF

9. Tables S3-S4 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

Enriched GSEA pathways

Published
2023
Full Text
View/download PDF

10. Tables S1-S2 from Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ERαWT and ERαMUT Breast Cancer

Author

Manav Korpal, Ping Zhu, Peter G. Smith, Markus Warmuth, Lihua Yu, Shihua Yao, Michael J. Wick, Suzanne Wardell, John Wang, Frédéric H. Vaillancourt, Michael Thomas, Vanitha Subramanian, Sasirekha Sivakumar, Amy Siu, Ricardo Ribas, Nathalie Rioux, Victoria Rimkunas, Dominic J. Reynolds, Sujatha Rajagopalan, Sudeep Prajapati, Sunil Pancholi, Morgan O'Shea, John Norris, Tuong-Vi Nguyen, Alyssa Moriarty, Diana Melchers, Lesley-Ann Martin, Crystal Mackenzie, Nicholas Larsen, Weidong G. Lai, Galina Kuznetsov, Pavan Kumar, Namita Kumar, Amy Kim, Craig Karr, Jaya J. Joshi, Sean Irwin, René Houtman, Andrew Hart, Ming-Hong Hao, Peter Fekkes, Sean Eckley, Subhasree Das, Benjamin Caleb, Silvia Buonamici, David M. Bolduc, Sergei Agoulnik, Kiran Aithal, Deepti Banka, Zhenhua J. Wu, Guo Zhu Zheng, Craig Furman, and Xiaoling Puyang

Abstract

Crystallography and amino acid coordinates

Published
2023
Full Text
View/download PDF

11. Covalent ERα Antagonist H3B-6545 Demonstrates Encouraging Preclinical Activity in Therapy-Resistant Breast Cancer

Author

Craig Furman, Xiaoling Puyang, Zhaojie Zhang, Zhenhua J. Wu, Deepti Banka, Kiran B. Aithal, Lee A. Albacker, Ming-Hong Hao, Sean Irwin, Amy Kim, Meagan Montesion, Alyssa D. Moriarty, Karthikeyan Murugesan, Tuong-Vi Nguyen, Victoria Rimkunas, Tarek Sahmoud, Michael J. Wick, Shihua Yao, Xun Zhang, Hao Zeng, Frédéric H. Vaillancourt, David M. Bolduc, Nicholas Larsen, Guo Zhu Zheng, Sudeep Prajapati, Ping Zhu, and Manav Korpal

Subjects
Clinical Trials as Topic, Cancer Research, Indazoles, Oncology, Pyridines, Estrogen Receptor alpha, Humans, Breast Neoplasms, Female, Neoplasm Recurrence, Local, Fulvestrant
Abstract

Nearly 30% of patients with relapsed breast cancer present activating mutations in estrogen receptor alpha (ERα) that confer partial resistance to existing endocrine-based therapies. We previously reported the development of H3B-5942, a covalent ERα antagonist that engages cysteine-530 (C530) to achieve potency against both wild-type (ERαWT) and mutant ERα (ERαMUT). Anticipating that the emergence of C530 mutations could promote resistance to H3B-5942, we applied structure-based drug design to improve the potency of the core scaffold to further enhance the antagonistic activity in addition to covalent engagement. This effort led to the development of the clinical candidate H3B-6545, a covalent antagonist that is potent against both ERαWT/MUT, and maintains potency even in the context of ERα C530 mutations. H3B-6545 demonstrates significant activity and superiority over standard-of-care fulvestrant across a panel of ERαWT and ERαMUT palbociclib sensitive and resistant models. In summary, the compelling preclinical activity of H3B-6545 supports its further development for the potential treatment of endocrine therapy–resistant ERα+ breast cancer harboring wild-type or mutant ESR1, as demonstrated by the ongoing clinical trials (NCT03250676, NCT04568902, NCT04288089). Summary: H3B-6545 is an ERα covalent antagonist that exhibits encouraging preclinical activity against CDK4/6i naïve and resistant ERαWT and ERαMUT tumors.

Published
2022
Full Text
View/download PDF

12. Abstract P1-10-08: Development of a first-in-class oral selective ERα covalent antagonist (SERCA) for the treatment of ERαWT and ERαMUT breast cancer

Author

Sean Irwin, Guo-Zhu Zheng, Sherri Smith, Craig Furman, Deepti Banka, Nathalie Rioux, Victoria Rimkunas, J Norris, Prashant Kumar, Nicholas A. Larsen, Y Yu, Anand Selvaraj, Sergei Agoulnik, Craig Karr, Andrew Hart, T Bowser, Lorna Helen Mitchell, Crystal MacKenzie, Huilan Yao, Pete Smith, Tarek Sahmoud, Peter Fekkes, Jiayi Wu, T-V Nguyen, Zhaojie Zhang, Frédéric H. Vaillancourt, Betty Chan, Mike Thomas, Benjamin Caleb, O'shea Morgan Welzel, Manav Korpal, Markus Warmuth, Ping Zhu, S Wardell, Amy K. Kim, Galina Kuznetsov, Sean Eckley, Allison Davis, Sudeep Prajapati, Jun Wang, Ming-Hong Hao, V. Subramanian, Naresh Kumar, Xiaoling Puyang, Lihua Yu, Jaya Julie Joshi, Reynolds Dominic, and G W Lai

Subjects
Cancer Research, Fulvestrant, Chemistry, Antagonist, Estrogen receptor, medicine.disease, Breast cancer, Oncology, Mechanism of action, Cancer research, medicine, medicine.symptom, Receptor, Estrogen receptor alpha, Tamoxifen, medicine.drug
Abstract

Mutations in estrogen receptor alpha (ERα) are detected in up to 30% of breast cancer patients who have relapsed during endocrine therapy. ERα mutations functionally confer resistance to existing classes of endocrine therapies, likely through gaining constitutive activity. The fact that current ER-directed therapies are only partially effective in the ERα mutant setting, and that a significant proportion of resistant breast cancer metastases continue to remain dependent on ERα signaling for growth/survival, highlights the critical need to develop the next generation of ERα antagonists that can overcome aberrant ERα activity. Using structure-based drug design approaches we have identified a novel class of ERα antagonist referred to as Selective ERα Covalent Antagonist (SERCA) that inactivate both wild-type and mutant ERα by targeting a unique cysteine residue that is not conserved among other steroid hormone receptors. Biophysical, biochemical and cellular analyses confirm the covalent mechanism of action, specific binding to ER and selective inhibition of ERα-dependent transcription of SERCAs. H3B-6545 is a highly selective SERCA that potently antagonizes wild-type and mutant ERα in biochemical and cell based assays demonstrating increased potency over standard of care and other experimental agents. In vivo, H3B-6545 shows superior efficacy to fulvestrant in the MCF-7 xenograft model with once daily oral dosing, achieving maximal antitumor activity at doses >10x below the maximum tolerated dose in mice. In addition, H3B-6545 shows superior antitumor activity to both tamoxifen and fulvestrant in patient derived xenograft models of breast cancer carrying estrogen receptor mutations. In summary, H3B-6545 is a first-in-class, orally available and selective ER covalent antagonist with a compelling pre-clinical profile that is being developed for the treatment of ERα positive breast cancer. Citation Format: Korpal M, Puyang X, Furman C, Zheng GZ, Banka D, Wu J, Zhang Z, Thomas M, Mackenzie C, Yao H, Rimkunas V, Kumar P, Caleb B, Karr C, Subramanian V, Irwin S, Larsen N, Vaillancourt F, Nguyen T-V, Davis A, Chan B, Hao MH, O'Shea M, Prajapati S, Agoulnik S, Kuznetsov G, Kumar N, Yu Y, Lai G, Hart A, Eckley S, Fekkes P, Bowser T, Joshi JJ, Selvaraj A, Wardell S, Norris J, Smith S, Reynolds D, Mitchell L, Wang J, Yu L, Kim A, Rioux N, Sahmoud T, Warmuth M, Smith PG, Zhu P. Development of a first-in-class oral selective ERα covalent antagonist (SERCA) for the treatment of ERαWT and ERαMUT breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-10-08.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results