Structure-based design of potent aromatase inhibitors by high-throughput docking.

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Caporuscio F, Rastelli G, Imbriano C, Del Rio A

Structure-based design of potent aromatase inhibitors by high-throughput docking.

J Med Chem. 2011 Jun 23;54(12):4006-17. doi: 10.1021/jm2000689. Epub 2011 May 23.

PubMed ID

21604760 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Letrozole	Cytochrome P450 19A1	IC 50 (nM)	4.2	N/A	N/A	Details