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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.

SUBMITTER: Wang X

PROVIDER: S-EPMC3631274 | biostudies-other | 2013 Mar

REPOSITORIES: biostudies-other

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The development of highly potent inhibitors for porcupine.

Wang Xiaolei X Moon Jesung J Dodge Michael E ME Pan Xinchao X Zhang Lishu L Hanson Jordan M JM Tuladhar Rubina R Ma Zhiqiang Z Shi Heping H Williams Noelle S NS Amatruda James F JF Carroll Thomas J TJ Lum Lawrence L Chen Chuo C

Journal of medicinal chemistry 20130319 6

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 poste ...[more]

PMID: 23477365

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