GSK2830371

製品コードS7573 バッチS757303

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H29ClN4O2S
分子量 461.02 CAS No. 1404456-53-6
Solubility (25°C)* 体外 DMSO 92 mg/mL (199.55 mM)
Ethanol 92 mg/mL warmed with 50ºC water bath (199.55 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GSK2830371 is an orally active, allosteric Wip1 phosphatase inhibitor with IC50 of 6 nM.
in vitro In the PPM1D-amplified MCF7 breast carcinoma cells, GSK2830371 increases the phosphorylation of multiple Wip1 substrates, including p53 (S15), Chk2 (T68), H2AX (S139) and ATM (S1981). GSK2830371 shows selective antiproliferative activity in a subset of lymphoid cell lines, all of which carry a wild-type TP53 allele. Furthermore, co-treatment of doxorubicin and GSK2830371 results in a synergistic antiproliferative effect in DOHH2 and MX-1 tumor cells. [1]
in vivo In vivo, GSK2830371 increases phosphorylation of Chk2 (T68) and p53 (S15) and decreases Wip1 protein concentrations in DOHH2 tumors. GSK2830371 (150 mg/kg p.o.) also inhibits the growth of DOHH2 tumor xenografts via inhibition of Wip1. [1]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro phosphatase assays
The primary in vitro Wip1 enzymatic assay measures fluorescence generated by Wip-1 (2–420) hydrolysis of fluorescein diphosphate (FDP). 50 μM FDP substrate with compound or DMSO is added at room temperature before addition of 10 nM Wip1 in assay buffer (50 mM TRIS, pH 7.5, 30 mM MgCl2, 0.8 mM CHAPS, 0.05 mg/ml BSA). Fluorescent signal is detected on a Spectramax microplate reader (485/530 nm).
細胞アッセイ 細胞株 36 TP53 wild-type cells and 25 TP53 mutant cells
濃度 ~10 μM
反応時間 7 days
実験の流れ Cells are seeded into 96 well plates at 200–400 cells per well and treated with a compound dilution series on day 1. After 7 d, The CellTiter-Glo cell viability assay is used to determine effects on cell growth. Luminescent signal is detected on an EnVision 2104.
動物実験 動物モデル Female SCID mice bearing DOHH2 tumor xenografts
投薬量 150 mg/kg BID
投与方法 p.o.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

NR2F1 is a barrier to dissemination of early stage breast cancer cells [ Cancer Res, 2022, canres.4145.2021] PubMed: 35471456
NR2F1 is a barrier to dissemination of early-stage breast cancer cells [ Cancer Res, 2022, 82 (12): 2313–2326.] PubMed: None
Substrate spectrum of PPM1D in the cellular response to DNA double-strand breaks [ iScience, 2022, 25(9):104892] PubMed: 36060052
CDK5RAP2 loss-of-function causes premature cell senescence via the GSK3β/β-catenin-WIP1 pathway [ Cell Death Dis, 2021, 13(1):9] PubMed: 34930892
WIP1 Promotes Cancer Stem Cell Properties by Inhibiting p38 MAPK in NSCLC [ Signal Transduct Target Ther, 2020, 15;5(1):36] PubMed: 32296033
[ Oncogene, 2020, ] PubMed: 32848211
Targeting Mutant PPM1D Sensitizes Diffuse Intrinsic Pontine Glioma Cells to the PARP Inhibitor Olaparib. [ Mol Cancer Res, 2020, 10.1158/1541-7786.MCR-19-0507] PubMed: 32229503
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma. [ Nat Commun, 2019, 10(1):3790] PubMed: 31439867
DNA Damage Signaling-Induced Cancer Cell Reprogramming as a Driver of Tumor Relapse [ Mol Cell, 2019, 74(4):651-663.e8] PubMed: 30954402
Genome-scale CRISPR-Cas9 screen identifies druggable dependencies in TP53 wild-type Ewing sarcoma [ J Exp Med, 2018, 215(8):2137-2155] PubMed: 30045945

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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