ZFIN ID: ZDB-PUB-130403-2
The development of highly potent inhibitors for porcupine
Wang, X., Moon, J., Dodge, M.E., Pan, X., Zhang, L., Hanson, J.M., Tuladhar, R., Ma, Z., Shi, H., Williams, N.S., Amatruda, J.F., Carroll, T.J., Lum, L., and Chen, C.
Date: 2013
Source: Journal of medicinal chemistry   56(6): 2700-2704 (Journal)
Registered Authors: Amatruda, James F., Moon, Jesung
Keywords: none
MeSH Terms:
  • Drug Discovery*
  • Enzyme Inhibitors/chemistry*
  • Enzyme Inhibitors/pharmacology*
  • Membrane Proteins/antagonists & inhibitors*
  • Small Molecule Libraries/chemistry*
  • Small Molecule Libraries/pharmacology*
  • Structure-Activity Relationship
PubMed: 23477365 Full text @ J. Med. Chem.

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.