Uses
2-((4-Oxo-3-phenyl-3,4,6,7-tetrahydrothieno[3,2-d]pyrimidin-2-yl)thio)-N-(5-phenylpyridin-2-yl)acetamide is an inhibitor of Porcupine, a member of the membrane-bound O-acyltransferase family of proteins.
Biological Activity
iwp-l6 is an inhibitor of porcupine with ic50 value of 0.5nm [1].iwp-l6 is developed as a sub-nanomolar inhibitor.of porcupine. it targets the wnt signaling since porcupine is the enzyme to catalyze the palmitoylation of wnt proteins. in hek293 cells, iwp-l6 is found to inhibi the phosphorylation of dishevelled 2 (dvl2) significantly. iwp-l6 has good stability in human plasma but weaker stability in rat and mouse plasma. in vivo assay shows that iwp-l6 is quite active in zebrafish. it blocks the regeneration of the tailfin effectively. it also shows inhibition of posterior axis formation at low micromolar concentrations. additionally, in cultured mouse embryonic kidneys, 10nm iwp-l6 can significantly reduce branching morphogenesis while 50nm iwp-l6 completely blocks wnt signaling [1].
References
[1] wang x, moon j, dodge me, pan x, zhang l, hanson jm, tuladhar r, ma z, shi h, williams ns, amatruda jf, carroll tj, lum l, chen c. the development of highly potent inhibitors for porcupine. j med chem. 2013 mar 28;56(6):2700-4.
