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Compounds Targetting Androgen Receptor to treat Castration Resistant Prostate Cancer

详细技术说明

None

*Abstract

BackgroundCastration-resistant prostate cancer (CRPC) is currently incurable and makes prostate cancer the second most common cause of cancer death among men in the United States. Multiple studies have shown that the androgen receptor (AR) is activated via multiple mechanisms including AR overexpression, mutation, hypersensitization, and/or intratumoral androgen synthesis in patients relapsed after androgen deprivation therapy (ADT). Overexpression and knockdown studies have shown that AR is a key molecular determinant and an excellent therapeutic target for CRPC.TechnologyInnovators at the University of Pittsburgh have identified novel small molecules that block the nuclear localization and function of the androgen receptor in CRPC cells. The compounds are not cytotoxic and decrease AR levels in CRPC cells. Xenograft studies using these small molecules showed inhibition of castration-resistant growth of C4-2 and 22Rv1 xenograft tumors in SCID mice. This work demonstrates the potential of these compounds in CRPC tumor therapy. A second class of compounds significantly decreases cell proliferation in AR-positive cell lines while they have no effect on proliferation in AR-negative cell lines.Application-Potential to inhibit endogenous AR signaling in CRPC cells -Potential to inhibit the growth of CRPC tumors -Potential to inhibit androgen dependent tumorsAdvantages-No cytotoxicity- Very effective in blocking AR nuclear localization-Lead compounds are effective against all tested AR-positive prostate cancer cell linesStage of Development In-vivo and In-vitro studies

*Principal Investigation

Name: Erin Skoda

Department: Chemistry

Name: Zhou Wang

Department: Med-Urology

Name: Peter Wipf, Professor

Department: Chemistry

国家/地区

美国