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We discover and develop novel, "best-in-class" inhibitors of CYP17, a validated metalloenzyme involved in prostate cancer.

Publications and Presentations

Publications and Presentations

Publications

Norris JD, Ellison SJ, Baker JG, Stagg DB, Wardell SE, Park S, Alley HM, Baldi RM, Yllanes A, Andreano KJ, Stice JP, Lawrence SA, Eisner JR, Price DK, Moore WR, Figg WD, McDonnell DP. Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer. J Clin Invest 2017;127(6):2326-2338

Maity SN, Titus MA, Revekka G, Wu G, Lu JF, Ramachandran, Li-Ning-Tapia M,  Logothetis J, Araujo JC, Efstathiou E.  Targeting of CYP17 A1 Lyase by VT-464 Inhibits Adrenal and Intratumoral Androgen Biosynthesis and Tumor Growth of Castration Resistant Prostate Cancer Nature Scientific Reports | 6:35354 | DOI: 10.1038/srep35354 (2016)

Rafferty SW, Eisner JR, Moore WR, Schotzinger RJ, Hoekstra WJ. Highly-selective 4-(1,2,3-triazole)-based P450c17a 17,20-lyase inhibitors. Bioorg Med Chem Lett 2014;24:2444–7.

Toren PJ, Kim S, Pham S, Mangalji A, Adomat H, Tomlinson Guns ES, Zoubeidi A, Moore W, Gleave ME. Anticancer Activity of a Novel Selective CYP17A1 Inhibitor in Preclinical Models of Castrate-Resistant Prostate Cancer. Mol Cancer Ther 2014;14(1);59–69

Presentations

Speers C, Chandler B, ZhaoSG, Liu M, Wilder-Romans K, Olsen E, Nyati S, Rae J, Hayes D, Spratt D, Wahl D, Feng FY, Pierce LJ. Radiosensitization of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) cells using seviteronel (SEVI), a selective CYP17 lyase and AR inhibitor. [2017 ASCO Annual Meeting]

Gucalp A, Danso M, Elias A, Bardia A, Ali H, Potter D, Gabrail N, Haley B, Khong H, Riley E, Ervin L, Eisner J, Baskin-Bey E, Moore W, Traina TA. Phase (Ph) 2 stage 1 clinical activity of seviteronel, a selective CYP17-lyase and androgen receptor (AR) inhibitor, in women with advanced AR+ triple-negative breast cancer (TNBC) or estrogen receptor (ER)+ BC : CLARITY-01. [2017 ASCO Annual Meeting]

Gordon MA, D’Amato N, Christenson J, Babbs B, Gu H, Wulfkuhle J, Petricoin E, Elias A, Richer JK. Synergy between androgen receptor (AR)-targeting agents seviteronel (SEVI) or enzalutamide (ENZA) and mTOR or HER2 pathway-targeting agents in breast cancer. [2017 AACR Annual Meeting]

Wardell SE, Yllanes AP, Norris JD, Stice JP, White H, Fleming RA, Strum JC, Moore WR, McDonnell DP. Effects of the selective CYP17-lyase and androgen receptor (AR) inhibitor, seviteronel, and the cyclin-dependent kinase (CDK) 4/6 inhibitor, G1T38, on tumor growth in an AR-V7+ castration-resistant prostate cancer (CRPC) xenograft model. [2017 AACR Annual Meeting]

Gucalp A, Bardia A, Gabrail N, DaCosta N, Danso M, Elias AD, Ali H, Lemon SJ, Riley EC,  Eisner       JR, Fleming RA, Kurman MR, Moore WR, Traina TA. Phase 1/2 study of oral seviteronel (VT-464), a dual    CYP17-lyase inhibitor and androgen receptor (AR) antagonist, in patients with advanced AR positive triple      negative (TNBC) or estrogen receptor (ER) positive breast cancer (BC). [2016 San Antonio Breast Cancer Symposium]

Peer CJ, Schmidt KT, Noguiera MAF, Eisner J, Fleming R, Moore W, Figg WD. Pharmacokinetic analysis of the oral CYP17 lyase inhibitor VT-464 to describe time-dependent changes in clearance in men with metastatic castrate-resistant prostate cancer [2016 The American Society for Clinical Pharmacology and Therapeutics Annual Meeting]

Bardia A, Dacosta NA, Gabrail NY, Lemon S, Danso MA, Ali HA, Fleming RA, Kurman MR, Eisner JR, Moore WR,  Gucalp A, Traina TA. Phase (Ph) 1 study of oral seviteronel (VT-464), a dual CYP17-Lyase (L) inhibitor and androgen receptor (AR) antagonist, in patients (pts) with advanced AR+ triple negative (TNBC) or estrogen receptor (ER)+ breast cancer (BC). J Clin Oncol 34, 2016 (suppl; abstr 1088) [2016 ASCO Annual Meeting]

Nordquist LT, Shore ND, De Bono JS, Gupta S, Berry WR, Gillessen S, Liu G, Vogelzang NJ, Efstathiou E, Fleming MT, George DJ, Araujo JC, Zhang J, Kurman MR, Eisner JR, Moore WR. Objective response of the dual CYP17-Lyase (L) inhibitor / androgen receptor (AR) antagonist, VT-464, in patients with CRPC. J Clin Oncol 34, 2016 (suppl 2S; abstr 273) [2016 Genitourinary Cancers Symposium]

Shore ND, Nordquist LT, Gupta S, Fleming MT, Berry WR, Zhang J, Kurman MR, Eisner JR, Moore WR. Once-nightly (QD) dual CYP17-Lyase (L) inhibitor / androgen receptor (AR) antagonist VT-464 in patients with CRPC. J Clin Oncol 34, 2016 (suppl 2S; abstr 343) [2016 Genitourinary Cancers Symposium]

Kurman MR, Sager P, Rudoltz MS, Eisner JR, Goodman D, Heyman E, Salvail D, Bell C, Moore WR. Cardiovascular safety profile of VT-464 in patients (pts) with castrate-resistant prostate cancer (CRPC). J Clin Oncol 34, 2016 (suppl 2S; abstr 198) [2016 Genitourinary Cancers Symposium]

Gucalp A, Hudis C, Norton L, Patil S, Kurman MR, Eisner JR, Moore WR, Traina TA. A phase 1/2 study of once-daily oral VT-464 in patients with advanced androgen receptor (AR) positive triple negative (TNBC) or estrogen receptor (ER) positive breast cancer (BC). Cancer Res Volume 76, Issue 4 Supplement, pp. OT2-01-03 [2015 San Antonio Breast Cancer Symposium]

Ellison SJ, Norris JD, Wardell S, Eisner JR, Hoekstra WJ, Stagg DB, Alley HM, Moore WR, McDonnell DP. Effects of the dual selective CYP17 lyase inhibitor and androgen receptor (AR) antagonist, VT-464, on AR+ and ER+ tumor models in vitro and in vivo. Volume 76, Issue 4 Supplement, pp. P3-14-04 [2015 San Antonio Breast Cancer Symposium]

De Bono JS, Pezaro CJ, Gillessen S, Shore ND, Nordquist LT, Efstathiou E, Araujo JC, Berry WR, Liu G,  Vogelzang NJ, Omlin AG, Schotzinger RJ, Eisner JR, Moore WR. The oral CYP17-Lyase (L) inhibitor VT-464 in patients with CRPC. J Clin Oncol 33, 2015 (suppl 7; abstr 187) [2015 Genitourinary Cancers Symposium]

Moore WR, Norris JD, Wardell S, Eisner JR, Hoekstra WJ, Schotzinger RJ, McDonnell DP. Direct effects of the selective CYP17 lyase (L) inhibitor, VT-464, on the androgen receptor (AR) and its oral activity in an F876L tumor mouse xenograft model. J Clin Oncol 33, 2015 (suppl 7; abstr 263) [2015 Genitourinary Cancers Symposium]

Toren PJ, Pham S, Kim S, Adomat H, Zoubeidi A, Moore W, Gleave ME. Anti-cancer activity of a novel CYP17 inhibitor in pre-clinical models of castrate resistant prostate cancer. [2014 American Urological Association Annual Meeting]

Maity SN, Titus M, Wu G, Lu J-F, Ramachandran S, Eisner JR, Rafferty SW, Schotzinger RJ, Moore WR, Logothetis CJ, Araujo JC, Efstathiou E. Efficacy of VT-464, a Novel Selective Inhibitor of Cytochrome P450 17,20 lyase, in Castrate-Resistant Prostate Cancer. [AACR 2013 Annual Conference].

Figg WD, Spencer SD, Pisle ST, Pressler HM, Troutman SM, Eisner JR, Rafferty SW, Schotzinger RJ, Moore WR. Activity of oral VT-464, a selective CYP17-lyase inhibitor, in the LNCaP prostate cancer xenograft.. J Clin Oncol 30, 2012 (suppl; abstr 4671) [2012 Genitourinary Cancers Symposium]

Eisner JR, Abbott DH, Bird IM, Rafferty SW, Moore WR, Schotzinger RJ. VT-464: A novel, selective inhibitor of P450c17(CYP17)-17,20 lyase for castration-refractory prostate cancer (CRPC). J Clin Oncol 30, 2012 (suppl 5; abstr 198) [2012 Genitourinary Cancers Symposium]