The Development of Highly Potent Inhibitors for Porcupine

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• 作者：Xiaolei Wang ; 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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：March 28, 2013
• 年：2013
• 卷：56
• 期：6
• 页码：2700-2704
• 全文大小：363K
• 年卷期：v.56,no.6(March 28, 2013)
• ISSN：1520-4804

文摘

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鈥揳ctivity 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.