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Published in final edited form as: Clin Cancer Res. 2013 Dec 4;20(4):791–798. doi: 10.1158/1078-0432.CCR-12-3601

Figure A - Schematic of the full-length androgen receptor (a) and exon structure of major splice variants (ARV7 (b) and ARV567 (c)). Domains of AR include the amino (N) terminal domain, the DNA binding domain (DBD), the hinge region (HR), and the carboxy (C) terminal ligand-binding domain (LBD). Mutations which occur in specific regions are indicated. Adapted from Green and colleagues (68) with permission from Elsevier.

Figure 1B - ADVANCES: Inhibition of AR ligand production: Inhibition of CYP17A by Abiraterone, Orteronel, Galeterone, VT474, or CFG920 suppresses testicular, adrenal and tumoral androgen synthesis. Galeterone can suppress CYP17A, antagonize androgens and reduce AR levels. Abiraterone at high doses can inhibit AR and HSD3B. AR degradation: AR can be destabilized through inhibition of HSP90 binding. AR-cofactor association: Peptidomimetics (e.g. D2) can disrupt AR interaction with cofactors, decreasing AR driven gene transcription. AR antagonism: Enzalutamide and ARN509 block ligand/receptor interactions at the LBD, reduce AR-DNA association and AR nuclear accumulation. EPI-001 blocks AR NTD-coactivator association and nuclear accumulation, and is active against truncated AR variants lacking the C terminal domain (CTD). Adapted from Knudsen K, et al (69)

Figure A - Schematic of the full-length androgen receptor (a) and exon structure of major splice variants (ARV7 (b) and ARV567 (c)). Domains of AR include the amino (N) terminal domain, the DNA binding domain (DBD), the hinge region (HR), and the carboxy (C) terminal ligand-binding domain (LBD). Mutations which occur in specific regions are indicated. Adapted from Green and colleagues (68) with permission from Elsevier.

Figure 1B - ADVANCES: Inhibition of AR ligand production: Inhibition of CYP17A by Abiraterone, Orteronel, Galeterone, VT474, or CFG920 suppresses testicular, adrenal and tumoral androgen synthesis. Galeterone can suppress CYP17A, antagonize androgens and reduce AR levels. Abiraterone at high doses can inhibit AR and HSD3B. AR degradation: AR can be destabilized through inhibition of HSP90 binding. AR-cofactor association: Peptidomimetics (e.g. D2) can disrupt AR interaction with cofactors, decreasing AR driven gene transcription. AR antagonism: Enzalutamide and ARN509 block ligand/receptor interactions at the LBD, reduce AR-DNA association and AR nuclear accumulation. EPI-001 blocks AR NTD-coactivator association and nuclear accumulation, and is active against truncated AR variants lacking the C terminal domain (CTD). Adapted from Knudsen K, et al (69)