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

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

  • ACS Med Chem Lett. 2015 Mar 11;6(5):523-7. doi: 10.1021/acsmedchemlett.5b00001.
Ashvinikumar V Gavai 1 Claude Quesnelle 1 Derek Norris 1 Wen-Ching Han 1 Patrice Gill 1 Weifang Shan 1 Aaron Balog 1 Ke Chen 2 Andrew Tebben 1 Richard Rampulla 1 Dauh-Rurng Wu 1 Yingru Zhang 1 Arvind Mathur 1 Ronald White 1 Anne Rose 1 Haiqing Wang 1 Zheng Yang 1 Asoka Ranasinghe 1 Celia D'Arienzo 1 Victor Guarino 1 Lan Xiao 1 Ching Su 1 Gerry Everlof 1 Vinod Arora 3 Ding Ren Shen 1 Mary Ellen Cvijic 1 Krista Menard 1 Mei-Li Wen 1 Jere Meredith 3 George Trainor 1 Louis J Lombardo 1 Richard Olson 3 Phil S Baran 2 John T Hunt 1 Gregory D Vite 1 Bruce S Fischer 1 Richard A Westhouse 1 Francis Y Lee 1
Affiliations

Affiliations

  • 1 Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
  • 2 Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
  • 3 Bristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Abstract

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.

Keywords

Notch inhibitor; SAR; T-acute lymphoblastic leukemia; triple-negative breast cancer; γ-secretase inhibitor.

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