PMID: 16515479Mar 7, 2006Paper

Estrogen receptors: molecular interactions, virtual screening and future prospects

Current Topics in Medicinal Chemistry
Andrew J S KnoxDavid G Lloyd

Abstract

Identification of the Estrogen Receptor (ER) as a key mediator of the proliferation of breast cancer, and its involvement in pathways leading to osteoporosis and coronary heart disease, has resulted in a surge to discover and design compounds with the ability to modulate its actions (SERMs). Concurrently, a dramatic increase in the number of crystal structures of the ER has led to a more in depth understanding of the governing mechanisms involved in ER modulation. Entwining computational techniques with the availability of 3D structural data, has allowed not only the rational design of potent inhibitors of the ER, but also its incorporation in Virtual Screening (VS) in the search for novel chemotypes that can modulate the ER. An important initial step in the VS process is to filter towards molecules that occupy similar chemical space to a set of known actives prior to docking. We illustrate through Principal Component Analysis (PCA) of 145 descriptors the region of chemical space antiestrogens occupy compared with 'drug-like' space. We also review all available studies involving validation of several docking algorithms utilizing the ER, ultimately focusing on analysis of Enrichment (E) rates and False Positive (FP) rates to ill...Continue Reading

Citations

Jul 1, 2006·Expert Opinion on Drug Discovery·Eric R ProssnitzTudor I Oprea
Aug 1, 2008·Expert Opinion on Drug Discovery·Andrew Js KnoxMary J Meegan
May 12, 2009·Drug Discovery Today·Ni AiSean Ekins
Apr 15, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Eric R ProssnitzJeffrey B Arterburn
Feb 12, 2008·Trends in Pharmacological Sciences·Eric R ProssnitzJeffrey B Arterburn
Sep 30, 2008·Journal of Enzyme Inhibition and Medicinal Chemistry·Mary J MeeganDavid G Lloyd
Dec 17, 2008·Organic & Biomolecular Chemistry·Sonsoles Martín-SantamaríaAna Ramos
Dec 2, 2006·The Journal of Organic Chemistry·Neola F McKinley, Donal F O'Shea

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