title: Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.
abstract: Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Michael F T
authors.initials: MF
authors.lastname: Koehler
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bergeron
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Edna F
authors.initials: EF
authors.lastname: Choo
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Lau
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Chudi
authors.initials: C
authors.lastname: Ndubaku
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Danette
authors.initials: D
authors.lastname: Dudley
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Paul
authors.initials: P
authors.lastname: Gibbons
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Brad E
authors.initials: BE
authors.lastname: Sleebs
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Carl S
authors.initials: CS
authors.lastname: Rye
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: George
authors.initials: G
authors.lastname: Nikolakopoulos
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Chinh
authors.initials: C
authors.lastname: Bui
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Sanji
authors.initials: S
authors.lastname: Kulasegaram
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Wilhelmus J A
authors.initials: WJ
authors.lastname: Kersten
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Czabotar
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Colman
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: David C S
authors.initials: DC
authors.lastname: Huang
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Baell
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Watson
authors.affiliation: AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hasvold
authors.affiliation: AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Zhi-Fu
authors.initials: ZF
authors.lastname: Tao
authors.affiliation: AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Souers
authors.affiliation: AbbVie, Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Elmore
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Flygare
authors.affiliation: Departments of Discovery Chemistry, Drug Metabolism and Pharmacokinetics, and Early Discovery Biochemistry, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Fairbrother
authors.affiliation: Walter and Eliza Hall Institute of Medical Research , 1G Royal Parade, Parkville, VIC 3052, Australia ; Department of Medical Biology, The University of Melbourne , Parkville, Victoria, Australia.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lessene
keywords: BCL-2; BCL-XL; apoptosis; cancer