Discovery of potent ligands for estrogen receptor beta by structure-based virtual screening.
With virtual screening based on a structure optimized through molecular dynamics (MD) and bioassays, 18 potent ligands of estrogen receptor (ER) beta were discovered from 70 purchased compounds here. Among them, dual profile was observed in two ligands (1a and 1b), as agonists for ERbeta and antagonists for ERalpha, and they might serve as lead compounds for selective ER modulators. The results also suggest that structures optimized through MD are applicable to lead discovery.
Shen
Jie
J
Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
Tan
Chengfang
C
Zhang
Yanyan
Y
Li
Xi
X
Li
Weihua
W
Huang
Jin
J
Shen
Xu
X
Tang
Yun
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D016208:Databases, Factual; D004354:Drug Screening Assays, Antitumor; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors*; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D020845:Selective Estrogen Receptor Modulators