Wnt-C59 (C59)S7037

Wnt-C59 (C59) is claimed to inhibit PORCN enzyme activity at nanomolar concentrations. Wnt-C59 (10 nM) blocks the palmitoylation-dependent Wnt–WLS interaction in HeLa cells transfected with either WNT3A-V5 or WNT8A-V5 plasmids. Wnt-C59 (100 nM) prevents incorporation of palmitate into WNT3A in HeLa cells transfected with WNT3A-V5, consistent with inhibition of PORCN activity. Wnt-C59 (100 nM) inhibits the activity of all splice variants of murine PORCN in PORCN-null HT1080 cells transfected with PORCN. Wnt-C59 is a nanomolar inhibitor of mammalian PORCN acyltransferase activity and blocks activation of all evaluated human Wnts. Wnt-C59 does not significantly inhibit the proliferation of any of 46 tested cancer cell lines in vitro at concentrations that completely inhibit PORCN. ^[1] Wnt-C59 is capable to significantly inhibit proliferation and comparable to the ICG-001 treated NMuMG (NMG) cells. Wnt-C59 inhibits sphere formation by threefold in NMuMG (NMG) cells, which is dependent on Wnt10b-secretion. Wnt-C59 inhibits proliferation of human MDA-MB 231 cells by >50%. ^[2] Wnt-C59 (a Porcupine inhibitor) blocks radiolabel incorporation of [¹²⁵I]iodo-pentadecanoate in mouse L-Wnt3a cells transfected with Flag-Porcupine. ^[3]