Structure-Based Design of Potent Aromatase Inhibitors by High-Throughput Docking

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• 作者：Fabiana Caporuscio ; Giulio Rastelli ; Carol Imbriano ; Alberto Del Rio
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：June 23, 2011
• 年：2011
• 卷：54
• 期：12
• 页码：4006-4017
• 全文大小：1107K
• 年卷期：v.54,no.12(June 23, 2011)
• ISSN：1520-4804

文摘

Cytochrome P450 aromatase catalyzes the conversion of androgen substrates into estrogens. Aromatase inhibitors (AIs) have been used as first-line drugs in the treatment of estrogen-dependent breast cancer in postmenopausal women. However, the search for new, more potent, and selective AIs still remains necessary to avoid the risk of possible resistances and reduce toxicity and side effects of current available drugs. The publication of a high resolution X-ray structure of human aromatase has opened the way to structure-based virtual screening to identify new small-molecule inhibitors with structural motifs different from all known AIs. In this context, a high-throughput docking protocol was set up and led to the identification of nanomolar AIs with new core structures.