The development of highly potent inhibitors for porcupine

  • J Med Chem. 2013 Mar 28;56(6):2700-4. doi: 10.1021/jm400159c.
Xiaolei Wang  1 ,  Jesung Moon ,  Michael E Dodge ,  Xinchao Pan ,  Lishu Zhang ,  Jordan M Hanson ,  Rubina Tuladhar ,  Zhiqiang Ma ,  Heping Shi ,  Noelle S Williams ,  James F Amatruda ,  Thomas J Carroll ,  Lawrence Lum ,  Chuo Chen
Affiliations
  • 1. Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
PMID: 23477365 DOI: 10.1021/jm400159c
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.

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