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Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors.

ABSTRACT: Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of ?-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as a candidate for clinical evaluation.

SUBMITTER: Gavai AV

PROVIDER: S-EPMC4434460 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Discovery of Clinical Candidate BMS-906024: A Potent Pan-Notch Inhibitor for the Treatment of Leukemia and Solid Tumors.

Gavai Ashvinikumar V AV Quesnelle Claude C Norris Derek D Han Wen-Ching WC Gill Patrice P Shan Weifang W Balog Aaron A Chen Ke K Tebben Andrew A Rampulla Richard R Wu Dauh-Rurng DR Zhang Yingru Y Mathur Arvind A White Ronald R Rose Anne A Wang Haiqing H Yang Zheng Z Ranasinghe Asoka A D'Arienzo Celia C Guarino Victor V Xiao Lan L Su Ching C Everlof Gerry G Arora Vinod V Shen Ding Ren DR Cvijic Mary Ellen ME Menard Krista K Wen Mei-Li ML Meredith Jere J Trainor George G Lombardo Louis J LJ Olson Richard R Baran Phil S PS Hunt John T JT Vite Gregory D GD Fischer Bruce S BS Westhouse Richard A RA Lee Francis Y FY

ACS medicinal chemistry letters 20150311 5

Structure-activity relationships in a series of (2-oxo-1,4-benzodiazepin-3-yl)-succinamides identified highly potent inhibitors of γ-secretase mediated signaling of Notch1/2/3/4 receptors. On the basis of its robust in vivo efficacy at tolerated doses in Notch driven leukemia and solid tumor xenograft models, 12 (BMS-906024) was selected as a candidate for clinical evaluation. ...[more]

PMID: 26005526

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