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CAS No.: 1243243-89-1

Wnt-C59 Catalog No. CSN13808

Synonyms: C59;PORCN Inhibitor II

Wnt-C59 is a potent inhibitor of PORCN, as measured by prevention of Wnt3A activation (IC50 = 74 pM).

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纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

生物活性

靶点 PORCN

IC50:~74pM
描述The up-regulated secretion of Wnt and the activation of Wnt signaling cascade are associated with tumorigenesis and metastasis. PORCN is a key enzyme in Wnt biosynthesis responsible for the palmitoylation (posttranslational acylation) of Wnt proteins. Wnt-C59 is a potent inhibitor of PORCN activity and Wnt/β-catenin signaling. In HEK293 cells constitutively expressing Wnts, the activation of β-catenin binding site-driven luciferase reporter was inhibited by Wnt-C59 with an IC50 of 74 pmol/l. The secretion of Wnt into the culture medium was blocked by 0.1 nmol/ Wnt-C59. The interaction between Wnt and WLS, a carrier protein required in Wnt acylation, was abrogated when cells were pretreated with 10 nmol/l Wnt-C59. The incorporation of palmitate into Wnt was inhibited when 100 nmol/l Wnt-C59 was added into the culture medium. Nine β-catenin activating Wnts and four additional noncanonical Wnts lost activity in cells treated with 10 nmol/l Wnt-C59. The half-life of Wnt in mice was around 1.94 hours after intravenous (2.5 mg/kg) or oral (5 mg/kg) administration. After one single oral dose, the blood concentration of Wnt-C59 maintained 10-fold above the in vitro IC50 for more than 16 hours. In mice orthotopically transplanted with independent MMTV-WNT1 tumors, the administration of 10 mg/kg/d Wnt-C59 for 17 days significantly suppressed the tumor growth compared with vehicle-treated mice. Wnt-C59 administration also significantly down-regulated the expression of β-catenin target gene, including Axin2, Ccnd1, c-Myc, and Tcf7. Together with the decrease of c-Myc and CyclinD, Wnt-C59 reduced the proliferation of carcinoma cells as indicated by Ki67 immunostaining. Moreover, Wnt-C59-treated mice exhibited markedly less β-catenin in cytoplasm and nucleus, whereas vehicle-treated group had abundant cytoplasmic and nuclear β-catenin.
作用机制Serine acylation in Wnt protein is essential in Wnt secretion. PORCN is a key enzyme that resides in the endoplasmic reticulum, adding palmitate to a serine in Wnt protein. Wnt-C59 acts as a nanomolar inhibitor of the acyltransferase activity of PORCN.
细胞研究

Cell Data

Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
human HT1080 cells	-	Function assay	-	Inhibition of porcupine activity (unknown origin) expressed in human HT1080 cells assessed as suppression of Wnt3A-mediated super top flash activity by STF luciferase assay, IC50=7.4e-05 μM.	26522946

动物研究
剂量
Mice: 2.5 mg/kg^[2] (i.v.); 5 mg/kg - 10 mg/kg^[1] (p.o.), 100 mg/kg^[3] (C57/BL6 Mice, p.o.)

给药途径
i.v., p.o.
参考文献

动物研究
剂量	Mice: 2.5 mg/kg^[2] (i.v.); 5 mg/kg - 10 mg/kg^[1] (p.o.), 100 mg/kg^[3] (C57/BL6 Mice, p.o.)
给药途径	i.v., p.o.

[1] Proffitt KD, Madan B, et al. Pharmacological inhibition of the Wnt acyltransferase PORCN prevents growth of WNT-driven mammary cancer. Cancer Res. 2013;73(2):502-7.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.6354 mL
- 13.1770 mL
- 26.3539 mL
- 5 mM
- 0.5271 mL
- 2.6354 mL
- 5.2708 mL
- 10 mM
- 0.2635 mL
- 1.3177 mL
- 2.6354 mL

技术信息

CAS号

1243243-89-1

储存条件

粉末: Keep in dark place,Inert atmosphere,Room temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C25H21N3O

运输

蓝冰

分子量

379.45

别名

C59;PORCN Inhibitor II

溶解度

DMSO	650.0 mg/mL (1713.0 mM) warming
Water	insoluble

动物实验配方

IP	2% DMSO+2% Tween80+40% PEG300+water	13 mg/mL	clear
PO	0.5% CMC-Na	55 mg/mL	suspension

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Wnt-C59 Catalog No. CSN13808

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