Drugs that target novel surfaces on the androgen receptor (AR) or that target novel AR regulatory mechanisms may prove effective in the treatment of castrate-resistant prostate cancer. Recently we reported a lead compound, termed MJC13, that inhibits AR function by preventing hormone-induced AR-chaperone complex dissociation and nuclear translocation. We demonstrated that MJC13 effectively blocks AR-dependent gene expression in cellular models of prostate cancer. Herein we report a structure-activity relationship study on MJC13. We prepared a series of MJC13 analogues in which we modified the 2,3-dichloroaniline moiety or the cyclohexyl moiety in an effort to improve pharmacokinetic properties while maintaining, or even improving, inhibition of AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation.  This series of analogues represents a discrete class of FKBP52-specific inhibitors to treat hormone-dependent diseases.

Structure-activity relationship study of a novel inhibitor of androgen receptor signaling, MJC13, using a series of aryl amides and ureas

244th National Meeting (2012)

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