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The development of highly potent inhibitors for porcupine

Xiaolei Wang; Jesung Moon; Michael E. Dodge; Xinchao Pan; Lishu Zhang; Jordan M. Hanson; Rubina Tuladhar; Zhiqiang Ma; Heping Shi; Noelle S. Williams; et al.

(Profiled Authors: James F Amatruda; Thomas J Carroll; Chuo Chen; Lawrence Lum; Noelle S Williams; Lishu Zhang; Heping Shi)

Journal of Medicinal Chemistry. 2013;56(6):2700-2704.


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. © 2013 American Chemical Society.

PMID: 23477365     PMCID: PMC3631274    

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