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English: Figure 2. AR signaling axis, and mechanisms of AR targeted inhibition. CYP17A1 is the enzyme responsible for the conversion of androgen precursors (i.e., pregnenolone and progesterone; represented by the light purple circles) to DHEA, while HSD3β1 converts DHEA to AD, AKR1C3 converts AD to testosterone (represented by the blue circles) and finally 5α-reductase converts testosterone to dihydrotestosterone (DHT; represented by the green circles). DHT-mediated activation of the AR causes a conformational change where the AR dimerizes, which then triggers AR translocation into the nucleus. Abiraterone selectively and irreversibly inhibits intratumoral androgen biosynthesis by potently blocking CYP17A1. As a result, less ligand is available for AR activation and AR axis signaling. Seviteronel (VT-464) is also an inhibitor of CYP17A1. Seviteronel has also been shown in preclinical models to have direct inhibitor effects on the AR. Enzalutamide is a potent second-generation antiandrogen that antagonizes the AR, prevents AR translocation into the nucleus, and inhibits AR-mediated transcription. Apalutamide (ARN-509) and darolutamide (ODM-201) are also potent, competitive AR inhibitors with similar mechanisms of action to enzalutamide. EPI-506 reduces AR transcriptional activity by inhibiting protein-protein interactions between the AR and its transcriptional co-regulators. JQ1 is a bromodomain inhibitor that limits AR transcriptional ability by targeting its coactivators. Abbreviations: AD, androstenedione; AKR1C3, aldo-keto reductase family 1 member C3; AR, androgen receptor; CYP17A1, cytochrome P450 c17; DHEA, dehydroepiandrosterone; D, dihydrotestosterone; HSP, heat shock protein; HSD3β1, human 3-beta-hydroxysteroid dehydroxynase/delta5-4 isomerase type 1; P, androgen precursors; PSA, prostate-specific antigen; T, testosterone.