Background:

TAK-700 R-form is a highly selective inhibitor of 17, 20-lyase with IC50 value of 38nM [1].

TAK-700 is a potent and selective inhibitor of the 17, 20-lyase activity of CYP17A1 which is responsible for androgen biosynthesis. Thus, TAK-700 is selected as a candidate for treatment of prostate cancer through reducing the adrenal androgen production. As an inhibitor of CYP17A1, the selectivity of TAK-700 is important to avoid causing the drug–drug interactions or side effects. TAK-700 shows potent inhibitory activity and high selectivity against 17, 20-lyase over other CYPs including 11-hydroxylase and CYP3A4. The IC50 values for 11-hydroxylase and CYP3A4 are above 1μM and above 10μM, respectively. Moreover, in a monkey model, the administration of TAK-700 is found to significantly reduce serum testosterone and DHEA levels [1].

参考文献:
[1] Kaku T, Hitaka T, Ojida A, et al. Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17, 20-lyase inhibitor with potential utility in the treatment of prostate cancer. Bioorganic & medicinal chemistry, 2011, 19(21): 6383-6399.