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GSK 2830371

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Chemical Structure| 1404456-53-6 同义名 : -
CAS号 : 1404456-53-6
货号 : A447126
分子式 : C23H29ClN4O2S
纯度 : 98%
分子量 : 461.02
MDL号 : MFCD28009442
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(108.46 mM)，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：

2% DMSO+30% PEG 300+5% Tween 80+dd water 10 mg/mL

生物活性
描述 The wild-type p53-induced phosphatase (Wip1, encoded by PPM1D), an oncogenic type 2C serine/threonine phosphatase common to multiple cancers, negatively regulates key proteins in the DNA damage–response pathway. GSK2830371 is the first orally active, allosteric inhibitor of Wip1 with an IC50 value of 6 nM. GSK2830371 potently inhibited Wip1 (2–420) dephosphorylation of FDP and the endogenous substrates phospho-p38 MAPK (T180) with IC50 values of 6 nM and 13 nM, respectively. In the PPM1D-amplified MCF7 breast carcinoma cells, treatment with GSK2830371 for 24 h increased phosphorylation of substrates in a concentration-dependent manner. Treatment of MX-1 and MCF7 cells (Wip1 amplified, p53 wild type) with GSK2830371 caused concentration-dependent effects in cell growth assays. In a 7-d cell growth assay, GSK2830371 showed antiproliferative activity in a subset of lymphoid cell lines, all of which carry a wild-type TP53 allele. Co-treatment of DOHH2 and MX-1 tumor cells with the combination of GSK2830371 with doxorubicin, an anticancer agent shown to induce DNA damage, resulted in a synergistic antiproliferative effect. Unexpectively, treatment with GSK2830371 for 24 h also produced a rapid decrease in Wip1 protein concentrations. In a pharmacodynamic assay, orally administered GSK2830371 increased phosphorylation of Chk2 (T68) and p53 (S15) and decreased Wip1 protein concentrations in DOHH2 tumors. Following 14 d of oral dosing at 150 mg per kg body weight, BID (twice daily) and TID (thrice daily), GSK2830371 inhibited the growth of DOHH2 tumor xenografts by 41% and 68%, respectively[2].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
Escherichia coli BL21 (DE3) pLysS cells Function assay Inhibition of His-tagged PPM1D (1 to 420 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) pLysS cells using Ac-VEPPLS(P)QETFSDLW-NH2 substrate, IC50=0.0863 μM 26358280
MCF7 cells Function assay 24 h Inhibition of cell proliferation of human MCF7 cells incubated for 24 hrs, IC50=9.5 μM 26358280
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.17mL

0.43mL

0.22mL

10.85mL

2.17mL

1.08mL

21.69mL

4.34mL

2.17mL
参考文献

[1]Gilmartin AG, Faitg TH, et al. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol. 2014 Mar;10(3):181-7.

[2]Gilmartin AG, Faitg TH, Richter M, et al. Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction. Nat Chem Biol. 2014;10(3):181‐187