同义名 :	-
	CAS号 :	113906-27-7
	货号 :	A557216
	分子式 :	C19H16N2O3
	纯度 :	98%
	分子量 :	320.34
	MDL号 :	MFCD12912438
	存储条件：	Pure form Inert atmosphere, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性

描述

The Wnt/beta-catenin pathway is a family of proteins that is implicated in many vital cellular functions such as stem cell regeneration and organogenesis[3]. PNU-74654 is an inhibitor of Wnt/β-catenin pathway with an IC50 of 129.8 μM in NCI-H295 cell. In NCI-H295 cells,PNU-74654 significantly decreases cell proliferation 96 h after treatment, increases early and late apoptosis, decreases nuclear beta-catenin accumulation, impairs CTNNB1/beta-catenin expression and increases beta-catenin target genes 48 h after treatment.In NCI-H295 cells, PNU-74654 decreases cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. The SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase are decreased in NCI-H295 cells after 48 h PNU-74654 treatment. In Y1 cells, PNU-74654 impairs corticosterone secretion 24 h after treatment but does not decrease cell viability[4]. PNU-74654 binds to β-catenin with a KD of 450 nM. The Tcf3/Tcf4-binding surface on β-catenin contains a well-defined hot spot around residues K435 and R469[5].PNU-74654 suppressed cell growth at an IC 50 of 122 ± 0.4 μmol/L and synergistically enhanced the antiproliferative activity of gemcitabine by modulating the Wnt pathway. Using a 3D cell culture model, we found that the PNU-74654 caused tumor shrinkage. It reduced the migration of MCF-7 cells (by an 18% reduction in invasive behavior) after the treatment with PNU-74654 through perturbation of E-cadherin and MMP3/9. PNU-74654/5-FU combination enhanced the percentages of cells in S-phase and significantly increased apoptosis. Moreover, this agent was able to inhibit the growth of tumor in a xenograft model, although this effect was more pronounced in the animals treated with PNU-74654 plus 5-FU[6].

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	3.12mL 0.62mL 0.31mL	15.61mL 3.12mL 1.56mL	31.22mL 6.24mL 3.12mL

参考文献

[1]Leal LF, Bueno AC, et al. Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis. Oncotarget. 2015 Dec 15;6(40):43016-32. [2]Trosset JY, Dalvit C, et al. Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins. 2006 Jul 1;64(1):60-7. [3] Nithya Krishnamurthy,et al. Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 2018 Jan;62:50-60. [4] Leal LF, et al. Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis. Oncotarget. 2015 Dec 15;6(40):43016-32. [5]Trosset JY, et al. Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins. 2006 Jul 1;64(1):60-7. [6]Farzad Rahmani,et al. PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway. J Cell Physiol. 2019 Aug;234(8):14123-14132.