title: 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 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.
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Ashvinikumar V
authors.initials: AV
authors.lastname: Gavai
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Claude
authors.initials: C
authors.lastname: Quesnelle
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Norris
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Wen-Ching
authors.initials: WC
authors.lastname: Han
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Patrice
authors.initials: P
authors.lastname: Gill
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Weifang
authors.initials: W
authors.lastname: Shan
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Balog
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tebben
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Rampulla
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Dauh-Rurng
authors.initials: DR
authors.lastname: Wu
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Yingru
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Arvind
authors.initials: A
authors.lastname: Mathur
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: White
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Anne
authors.initials: A
authors.lastname: Rose
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Asoka
authors.initials: A
authors.lastname: Ranasinghe
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Celia
authors.initials: C
authors.lastname: D'Arienzo
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Victor
authors.initials: V
authors.lastname: Guarino
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Ching
authors.initials: C
authors.lastname: Su
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Gerry
authors.initials: G
authors.lastname: Everlof
authors.affiliation: Bristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Vinod
authors.initials: V
authors.lastname: Arora
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Ding Ren
authors.initials: DR
authors.lastname: Shen
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Mary Ellen
authors.initials: ME
authors.lastname: Cvijic
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Krista
authors.initials: K
authors.lastname: Menard
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Wen
authors.affiliation: Bristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Jere
authors.initials: J
authors.lastname: Meredith
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: George
authors.initials: G
authors.lastname: Trainor
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Lombardo
authors.affiliation: Bristol-Myers Squibb Research and Development , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Olson
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Vite
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Fischer
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Westhouse
authors.affiliation: Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543, United States.
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Lee
keywords: Notch inhibitor; SAR; T-acute lymphoblastic leukemia; triple-negative breast cancer; γ-secretase inhibitor