Discovery and structure-activity analysis of selective estrogen receptor modulators via similarity-based virtual screening.

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Shen J, Jiang J, Kuang G, Tan C, Liu G, Huang J, Tang Y

Discovery and structure-activity analysis of selective estrogen receptor modulators via similarity-based virtual screening.

Eur J Med Chem. 2012 Aug;54:188-96. doi: 10.1016/j.ejmech.2012.04.041. Epub 2012 May 14.

PubMed ID
22647217 [ View in PubMed
]
Abstract

A number of selective estrogen receptor modulators (SERMs) were discovered from the SPECS database via a simple protocol. Based on two reference SERMs we identified via structure-based virtual screening previously, ligand-based similarity search and molecular docking filtering were conducted to identify novel SERMs from SPECS library. Among the 36 purchased compounds, 21 were confirmed to be active by in vitro assays, and 10 showed dual profile properties, namely as antagonists of ERalpha and agonists of ERbeta. The anti-proliferative potency of these ligands was also evaluated against MCF-7 cell lines. Further investigation of the anti-proliferative mechanism of compound 3a suggested that it induced a G1 cell cycle arrest in ERalpha positive MCF-7 cell through ERalpha mediated cyclin D1 down-regulation.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
EstradiolEstrogen receptor alphaEC 50 (nM)1.05N/AN/ADetails
EstradiolEstrogen receptor alphaEC 50 (nM)0.05N/AN/ADetails
EstradiolEstrogen receptor betaEC 50 (nM)1.08N/AN/ADetails
EstradiolEstrogen receptor betaEC 50 (nM)0.036N/AN/ADetails
TamoxifenEstrogen receptor alphaIC 50 (nM)2540N/AN/ADetails
TamoxifenEstrogen receptor betaIC 50 (nM)1660N/AN/ADetails