title: The development of highly potent inhibitors for porcupine.
abstract: Porcupine is a member of the membrane-bound O-acyltransferase family of proteins. It catalyzes the palmitoylation of Wnt proteins, a process required for their secretion and activity. We recently disclosed a class of small molecules (IWPs) as the first reported Porcn inhibitors. We now describe the structure-activity relationship studies and the identification of subnanomolar inhibitors. We also report herein the effects of IWPs on Wnt-dependent developmental processes, including zebrafish posterior axis formation and kidney tubule formation.
authors.affiliation: Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Wang
authors.forename: Jesung
authors.initials: J
authors.lastname: Moon
authors.forename: Michael E
authors.initials: ME
authors.lastname: Dodge
authors.forename: Xinchao
authors.initials: X
authors.lastname: Pan
authors.forename: Lishu
authors.initials: L
authors.lastname: Zhang
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Hanson
authors.forename: Rubina
authors.initials: R
authors.lastname: Tuladhar
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.forename: Heping
authors.initials: H
authors.lastname: Shi
authors.forename: Noelle S
authors.initials: NS
authors.lastname: Williams
authors.forename: James F
authors.initials: JF
authors.lastname: Amatruda
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carroll
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lum
authors.forename: Chuo
authors.initials: C
authors.lastname: Chen
mesh_terms: D000217:Acyltransferases; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D054852:Small Molecule Libraries; D000217:Acyltransferases; C491188:PORCN protein, human