Seviteronel
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| Other names | VT-464 |
| Routes of administration | Oral |
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| Formula | C18H17F4N3O3 |
| Molar mass | 399.339493 g/mol g·mol−1 |
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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.[1][2][3][4][5][6] 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.[2][3][4][5][6] 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.[5] In addition, in in vitro models, seviteronel appears to possess greater efficacy as an antiandrogen relative to abiraterone.[4] Similarly to abiraterone acetate, seviteronel has also been found to act to some extent as an antagonist of the androgen receptor.[4]
As of June 2014, seviteronel has reached phase II clinical trials for prostate cancer.[3] In January 2016, it was designated fast-track status by the U.S. FDA.[7]
See also
References
- ^ Yin L, Hu Q, Hartmann RW (2013). "Recent progress in pharmaceutical therapies for castration-resistant prostate cancer". Int J Mol Sci. 14 (7): 13958–78. doi:10.3390/ijms140713958. PMC 3742227. PMID 23880851.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Stein MN, Patel N, Bershadskiy A, Sokoloff A, Singer EA (2014). "Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer". Asian J. Androl. 16 (3): 387–400. doi:10.4103/1008-682X.129133. PMC 4023364. PMID 24759590.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b c Rafferty SW, Eisner JR, Moore WR, Schotzinger RJ, Hoekstra WJ (2014). "Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors". Bioorg. Med. Chem. Lett. 24 (11): 2444–7. doi:10.1016/j.bmcl.2014.04.024. PMID 24775307.
- ^ a b c d Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Guns ES, Zoubeidi A, Moore W, Gleave ME (2015). "Anticancer activity of a novel selective CYP17A1 inhibitor in preclinical models of castrate-resistant prostate cancer". Mol. Cancer Ther. 14 (1): 59–69. doi:10.1158/1535-7163.MCT-14-0521. PMID 25351916.
- ^ a b c Stephen Neidle (30 September 2013). Cancer Drug Design and Discovery. Academic Press. pp. 341–342. ISBN 978-0-12-397228-6.
- ^ a b Wm Kevin Kelly; Edouard J. Trabulsi, MD; Nicholas G. Zaorsky, MD (17 December 2014). Prostate Cancer: A Multidisciplinary Approach to Diagnosis and Management. Demos Medical Publishing. pp. 342–. ISBN 978-1-936287-59-8.
- ^ [1]
Further reading
- Gomez L, Kovac JR, Lamb DJ (2015). "CYP17A1 inhibitors in castration-resistant prostate cancer". Steroids. 95: 80–7. doi:10.1016/j.steroids.2014.12.021. PMID 25560485.
- Bambury RM, Rathkopf DE (2015). "Novel and next-generation androgen receptor-directed therapies for prostate cancer: Beyond abiraterone and enzalutamide". Urol. Oncol. doi:10.1016/j.urolonc.2015.05.025. PMID 26162486.