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Mol Cell Endocrinol. 2012 Apr 16;352(1-2):79-91. doi: 10.1016/j.mce.2011.06.002. Epub 2011 Jun 16.

Recent developments in antiandrogens and selective androgen receptor modulators.

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TRG Oncology, Global Drug Discovery, Bayer HealthCare, D-13342 Berlin, Germany.


The androgens testosterone and dihydrotestosterone play an essential role in the development and maintenance of primary and secondary male characteristics. Androgens bind to a specific androgen receptor (AR), a ligand-dependent transcription factor which controls the expression of a large number of downstream target genes. The AR is an essential player in early and late prostate cancer, and may also be involved in some forms of breast cancer. It also represents a drug target for the treatment of hypogonadism. Recent studies furthermore indicate that targeting the AR in pathologies such as frailty syndrome, cachexia or polycystic ovary syndrome may have clinical benefit. Numerous AR ligands with very different pharmacological properties have been identified in the last 40 years and helped to treat several of these diseases. However, progress still needs to be made in order to find compounds with an improved profile with regard to efficacy, differentiation and side-effects. This will only be achieved through a better understanding of the mechanisms involved in normal and aberrant AR signaling.

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