PORCN酶活性和WNT抑制剂(WNT-C59)-abs810639

一、产品概述

二、产品信息

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. 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%. Wnt-C59 (a Porcupine inhibitor) blocks radiolabel incorporation of iodo-pentadecanoate in mouse L-Wnt3a cells transfected with Flag-Porcupine.

Wnt-C59 concentration remains greater than 10-fold above the in vitro IC50 for at least 16 hours following a single oral dose (5 mg/kg) in mice. Wnt-C59 (10 mg/kg) prevents growth of MMTV-WNT1 tumors in female nude mice orthotopically transplanted with independent MMTV-WNT1 tumors. Wnt-C59 (10 mg/kg) decreases Wnt pathway activity and decreased proliferation in MMTV-WNT1 tumors in female nude mice orthotopically transplanted with independent MMTV-WNT1 tumors as evident by decreased expression of β-catenin target gene expression. Wnt-C59 (10%) topically administered 4 weeks decreases the size of dysplasia of SmoM2-expressing cells in adult K14CREER/Rosa–SmoM2 mice.

三、背景

四、制备和贮存

五、产品特点

六、注意事项