title: The discovery of novel tartrate-based TNF-alpha converting enzyme (TACE) inhibitors.
abstract: A novel series of TNF-alpha convertase (TACE) inhibitors which are non-hydroxamate have been discovered. These compounds are bis-amides of L-tartaric acid (tartrate) and coordinate to the active site zinc in a tridentate manner. They are selective for TACE over other MMP's. We report the first X-ray crystal structure for a tartrate-based TACE inhibitor.
authors.affiliation: Department of Medicinal Chemistry, Schering-Plough Research Institute Cambridge, 320 Bent Street, Cambridge, MA 02141, United States.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Rosner
authors.forename: Zhuyan
authors.initials: Z
authors.lastname: Guo
authors.forename: Peter
authors.initials: P
authors.lastname: Orth
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Shipps
authors.forename: David B
authors.initials: DB
authors.lastname: Belanger
authors.forename: Tin Yau
authors.initials: TY
authors.lastname: Chan
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Curran
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Dai
authors.forename: Yongqi
authors.initials: Y
authors.lastname: Deng
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Girijavallabhan
authors.forename: Liwu
authors.initials: L
authors.lastname: Hong
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lavey
authors.forename: Joe F
authors.initials: JF
authors.lastname: Lee
authors.forename: Dansu
authors.initials: D
authors.lastname: Li
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Liu
authors.forename: Janeta
authors.initials: J
authors.lastname: Popovici-Muller
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.forename: Henry
authors.initials: H
authors.lastname: Vaccaro
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yu
authors.forename: Guowei
authors.initials: G
authors.lastname: Zhou
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Niu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Kozlowski
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lundell
authors.forename: Vincent
authors.initials: V
authors.lastname: Madison
authors.forename: Brian
authors.initials: B
authors.lastname: McKittrick
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: M
authors.initials: M
authors.lastname: Arshad Siddiqui
authors.forename: Corey O
authors.initials: CO
authors.lastname: Strickland
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000072198:ADAM17 Protein; D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013644:Tartrates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D011480:Protease Inhibitors; D013644:Tartrates; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human