Discovery of novel androgen receptor antagonists: a hybrid approach of pharmacophore-based and docking-based virtual screening.
Androgen receptor (AR) is an attractive target for the treatment of prostate cancer. An integrated pharmacophore-based and docking-based virtual screening approach was applied to identify novel AR antagonists with a distinct scaffold. The candidate compounds were evaluated for their abilities to inhibit prostate cancer cell proliferation and AR target gene prostate-specific antigen gene expression as well as the binding affinity to AR. A potent lead compound, T3, was discovered with the ability to inhibit prostate-specific antigen expression, with a similar binding affinity to AR, and with antiproliferative effects on AR-positive prostate cancer cells similar to that of MDV3100.
aKey Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Shandong, People's Republic of China bGraduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan cThe Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Jianzhen
J
Liu
Bo
B
Liu
Guangzhu
G
Guo
Yongkui
Y
Jing
Guisen
G
Zhao
D059002:Androgen Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D062126:Databases, Chemical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D062105:Molecular Docking Simulation; D009154:Mutation; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms; D011487:Protein Conformation; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship
D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D009570:Nitriles; D011720:Pyrazoles; D011725:Pyridines; D011944:Receptors, Androgen