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World J Urol. 2012 Jun;30(3):311-8. doi: 10.1007/s00345-011-0745-5. Epub 2011 Aug 11.

Advances in small molecule inhibitors of androgen receptor for the treatment of advanced prostate cancer.

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Genome Sciences Centre, BC Cancer Agency, 675 West 10th Avenue, Vancouver, BC, V5Z 1L3, Canada.



Current treatments for localized prostate cancer include brachytherapy, external beam radiation, surgery, and active surveillance. Unfortunately, 20-40% of prostate cancer patients will experience recurrence and require hormonal therapies. These therapies involve androgen ablation by chemical or surgical castration and application of antiandrogens. Hormonal therapy is initially effective, but will inevitably fail and the disease will progress to lethal castration-resistant prostate cancer (CRPC) from which patients succumb within 2 years. CRPC is considered to be dependent on transcriptionally active androgen receptors (AR). This article reviews recent advances in the discovery and development of small molecule inhibitors of AR.


A PubMed database search was performed for articles focused on small molecule inhibitors of AR for potential development for the treatment of prostate cancer. Compounds with broad effects on other pathways were not included.


Currently, there are several novel antiandrogens being tested in the clinic that have improved affinity for the AR and work by different mechanisms to the current battery of approved antiandrogens that are discussed. Small molecule inhibitors that interact with regions other than the AR ligand-binding pocket have been also been discovered. These small molecules include allosteric inhibitors of the LBD, compounds that alter AR conformation, and antagonists to the AR NTD and are highlighted.


CRPC is dependent upon transcriptionally active AR. Survival improvement may be achieved by complete blockade of all AR activity using novel small molecule inhibitors with unique mechanisms of action.

[Indexed for MEDLINE]

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