(S)-seviteronel

Seviteronel (INN; developmental code VT-464) is an experimental cancer treatment for a type of prostate cancer. It is being developed by Viamet Pharmaceuticals/Innocrin Pharmaceuticals.
Seviteronel is a non-steroidal antiandrogen, acting specifically as an androgen synthesis inhibitor via inhibition of the enzyme CYP17A1, for the treatment of castration-resistant prostate cancer. It has approximately 10-fold selectivity for the inhibition of 17,20-lyase (IC50 = 69 nM) over 17α-hydroxylase (IC50 = 670 nM), which results in less interference with corticosteroid production relative to the approved CYP17A1 inhibitor abiraterone acetate (which must be administered in combination with prednisone to avoid glucocorticoid deficiency and mineralocorticoid excess due to 17α-hydroxylase inhibition) and hence may be administerable without a concomitant exogenous glucocorticoid. Seviteronel is 58-fold more selective for inhibition of 17,20-lyase than abiraterone, which has IC50 values for inhibition of 17,20-lyase and 17α-hydroxylase of 15 nM and 2.5 nM, respectively. In addition, in in vitro models, seviteronel appears to possess greater efficacy as an antiandrogen relative to abiraterone. Similarly to abiraterone acetate, seviteronel has also been found to act to some extent as an antagonist of the androgen receptor.
As of June 2014, seviteronel has reached phase II clinical trials for prostate cancer. In January 2016, it was designated fast-track status by the U.S. FDA.

1.Synthesis Route

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