title: Identification of potent and selective TACE inhibitors via the S1 pocket.
abstract: By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Condon
authors.forename: Diane
authors.initials: D
authors.lastname: Joseph-McCarthy
authors.forename: Jeremy I
authors.initials: JI
authors.lastname: Levin
authors.forename: Henry-Georges
authors.initials: HG
authors.lastname: Lombart
authors.forename: Frank E
authors.initials: FE
authors.lastname: Lovering
authors.forename: Linhong
authors.initials: L
authors.lastname: Sun
authors.forename: Weiheng
authors.initials: W
authors.lastname: Wang
authors.forename: Weixin
authors.initials: W
authors.lastname: Xu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D000072198:ADAM17 Protein; D018360:Crystallography, X-Ray; D008024:Ligands; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000737:chemistry; D011480:Protease Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D013450:Sulfones / Q000737:chemistry
chemical_list: D008024:Ligands; D010880:Piperidines; D011480:Protease Inhibitors; D013450:Sulfones; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein