Seviteronel

Research use only, not for human use.

Seviteronel (VT-464) is a novel CYP17 cleavage enzyme inhibitor and androgen receptor antagonist used in breast and prostate cancer research.

Seviteronel (VT-464) is a potent CYP17 lyase inhibitor(h-Lyase IC50=69 nM) that demonstrated both exceptional in vitro lyase/hydroxylase selectivity (~10-fold) and oral activity in a hamster model of androgen biosynthesis inhibition.

Seviteronel (VT-464), a non-steroidal small molecule inhibits androgen production without mineralocorticoid excess or cortisol depletion by selective inhibition of CYP17 17,20-lyase. We determined the impact of Seviteronel (VT-464) on tumor growth of a mCRPC xenograft, MDA-PCa-133, in vivo, and on androgen signaling in C4-2B prostate cancer cells in vitro.

The MDA-PCa-133 xenograft is derived from a clinical CRPC bone metastasis. Subcutaneous MDA-PCa-133 tumor expresses PSA, full-length androgen receptor (AR) and AR-V7 isoform. We determined the effect of Seviteronel (VT-464) and AA on MDA-PCa-133 growing in tumor-bearing castrated male mice: randomization into three groups; oral treatment with vehicle only, VT-464, (100 mg/kg bid), or AA (100 mg/kg bid) for 25 days. Both Seviteronel (VT-464)and AA reduced tumor volume (>two fold compared to vehicle; p<0.05). These results indicate that selective Seviteronel (VT-464)CYP17 lyase inhibition is as effective as AA CYP17 inhibition in this model .

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Metabolic Enzyme/Protease

P450

P450 | Androgen Receptor

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1610537-15-9

399.34

C18H17F4N3O3

>98% (HPLC)

In Vitro:?DMSO : ≥ 50 mg/mL (125.21 mM)

CC(C)[C@@](O)(c1c[nH]nn1)c1ccc2cc(OC(F)F)c(OC(F)F)cc2c1

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(-20℃)

With Ice Pack

≥ 2 years