Development of anti-androgen ARN-509 1 ARN-509: a novel anti-androgen for prostate cancer treatment
نویسندگان
چکیده
Nicola J. Clegg, John Wongvipat, Jim Joseph, Chris Tran, Samedy Ouk, Anna Dilhas, Yu Chen, Kate Grillot, Eric D. Bischoff , Ling Cai, Anna Aparicio, Steven Dorow, Vivek Arora, Gang Shao, Jing Qian, Hong Zhao, Guangbin Yang, Chunyan Cao, John Sensintaffar, Teresa Wasielewska, Mark R. Herbert, Celine Bonnefous, Beatrice Darimont, Howard I. Scher, Peter Smith-Jones, Mark Klang, Nicholas D. Smith, Elisa De Stanchina, Nian Wu, Ouathek Ouerfelli, Peter J. Rix, Richard A. Heyman, Michael E. Jung, Charles L. Sawyers Jeffrey H. Hager Human Oncology & Pathogenesis Program & Howard Hughes Medical Institute, Organic Synthesis Core Facility, Molecular Pharmacology & Chemistry, Research Pharmacy Core Facility, Antitumor Assessment Core Facility, Analytical Pharmacology Core Facility, Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; Aragon Pharmaceuticals, Inc., San Diego, CA 92130.
منابع مشابه
A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509.
UNLABELLED Despite the impressive clinical activity of the second-generation antiandrogens enzalutamide and ARN-509 in patients with prostate cancer, acquired resistance invariably emerges. To identify the molecular mechanisms underlying acquired resistance, we developed and characterized cell lines resistant to ARN-509 and enzalutamide. In a subset of cell lines, ARN-509 and enzalutamide exhib...
متن کاملARN-509: a novel antiandrogen for prostate cancer treatment.
Continued reliance on the androgen receptor (AR) is now understood as a core mechanism in castration-resistant prostate cancer (CRPC), the most advanced form of this disease. While established and novel AR pathway-targeting agents display clinical efficacy in metastatic CRPC, dose-limiting side effects remain problematic for all current agents. In this study, we report the discovery and develop...
متن کاملPreclinical Development of ONC1-13B, Novel Antiandrogen for Prostate Cancer Treatment
Recently new drugs targeting androgen-dependent axis have been approved for the treatment of castration-resistant prostate cancer (CRPC) - Zytiga and Xtandi (formerly MDV3100), several other candidates (for example, ARN-509) are in early phases of clinical trials. However despite significant improvement in overall survival with new treatments it is evident that resistance to these drugs develop...
متن کاملResistance emerges to second-generation antiandrogens in prostate cancer.
The appearance of a mutant androgen receptor, AR(F876L), in prostate cancer cells chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist to agonist receptor function, undermining the potential long-term effectiveness of these second-generation antiandrogen drugs.
متن کاملDiscovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies
Activation of androgen receptor (AR) is crucial for prostate cancer growth. Remarkably, also castration-resistant prostate cancer (CRPC) is dependent on functional AR, and several mechanisms have been proposed to explain the addiction. Known causes of CRPC include gene amplification and overexpression as well as point mutations of AR. We report here the pharmacological profile of ODM-201, a nov...
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تاریخ انتشار 2012