XAV-939

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Chemical Structure| 284028-89-3 同义名 : NVP-XAV939
CAS号 : 284028-89-3
货号 : A180960
分子式 : C14H11F3N2OS
纯度 : 99%+
分子量 : 312.31
MDL号 : MFCD16879017
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 15 mg/mL(48.03 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

4% DMSO+corn oil 1 mg/mL

生物活性
描述 Poly (ADP-ribose) polymerase (PARP) 1 is an essential molecule in DNA damage response by sensing DNA damage and docking DNA repair proteins on the damaged DNA site through a type of posttranslational modification, poly (ADP-Ribosyl)ation (PARylation). PARP inhibitors, which inhibit PARylation through competitively binding to NAD+ binding site of PARP1 and PARP2, have improved clinical benefits for BRCA mutated tumors, leading to their accelerated clinical application[3]. XAV-939 is a potent tankyrase inhibitor that targets Wnt/β-catenin signaling. XAV-939 stabilizes axin by inhibiting tankyrase 1 and tankyrase 2 (IC50s of 5 and 2 nM, respectively), thereby stimulating β-catenin degradation. XAV939 binds tightly to the catalytic (PARP) domains of TNKS1 and TNKS2 (Kds of 99 and 93 nM, respectively)[4].XAV939 (0.5 μM, 1.0 μM) reduces DNA-PKcs protein levels 50% of the relative DMSO control in human lymphoblasts[5]. XAV939 induces a second wave of pro-cardiomyocyte gene expression as shown by increased Mesp1 and Isl1expression 2 to 4 days after Wnt inhibition, and by increased Nkx2.5 expression 4 to 6 days after XAV939 addition[6]. XAV-939 (10 nM) has a suppressive effect on elevated MMP-13 levels in both IL-1β-induced SW 1353 cells. XAV-939 (3 mL, 10 nM) has a suppressive effect on elevated MMP-13 levels in the rat OA model[7].XAV-939(1mg/mL,i.p.) ameliorates the psoriasiform skin disease induced by IMQ. XAV-939 results in a significant decrease in the IMQ-induced epidermal hyperplasia (indicated by acanthosis) and dermal inflammatory infiltrates in mice[8].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
DLD1 20 μM Function Assay 24 h Inhibition of tankyrase assessed as inhibition of TCF-dependent transcriptional activity 24527792
DLD1 20 μM Cytotoxic Assay 10 d Cytotoxicity assessed as growth inhibition 24527792
HEK293T Function Assay Inhibition of Wnt signaling assessed as inhibition of forskolin-induced cAMP response element activation with IC50 of 0.078 μM 23879431
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.20mL

0.64mL

0.32mL

16.01mL

3.20mL

1.60mL

32.02mL

6.40mL

3.20mL
参考文献

[1] Ahrum Min ,et al. PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation. Cancers (Basel). 2020 Feb 8;12(2):394.

[2] Huang SM, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-620.

[3] Ahrum Min ,et al. PARP Inhibitors as Therapeutics: Beyond Modulation of PARylation. Cancers (Basel). 2020 Feb 8;12(2):394.

[4] Huang SM, et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature. 2009 Oct 1;461(7264):614-620.

[5]Dregalla RC, et al. Regulatory roles of tankyrase 1 at telomeres and in DNA repair: suppression of T-SCE and stabilization of DNA-PKcs. Aging (Albany NY). 2010 Oct;2(10):691-708.

[6]Ao A, et al. DMH1, a Novel BMP Small Molecule Inhibitor, Increases Cardiomyocyte Progenitors and Promotes Cardiac Differentiation in Mouse Embryonic Stem Cells.,PLoS One. 2012;7(7):e41627.