STRUCTURE OF HUMAN MEMBRANE CYTOCHROME P450 INVOLVED IN ANDROGEN BIOSYNTHESIS

$1,927P41FY2011RRNIH

Stanford University, Stanford CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There are currently no structures of this important enzyme involved in androgen (and estrogen) synthesis. 80% of prostate cancers are dependent on androgens. Inhibitors of this cytochrome P450 are currently in clinical trials for prostate and breast cancer. We have crystals of the human enzyme in complex with one of the leading clinical trial candidates. This structure will allow us to improve current inhibitors and to use structure-based drug design to improve/design other inhibitors to increase selectivity and improve cancer treatment.

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