TH588

製品コードS7632 バッチS763202

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₃H₁₂Cl₂N₄
	分子量	295.17	CAS No.	1609960-31-7
Solubility (25°C)*	体外	DMSO	30 mg/mL warmed with 50ºC water bath (101.63 mM)
		Ethanol	1 mg/mL warmed with 50ºC water bath (3.38 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	TH588 is a potent and selective MTH1 (NUDT1) inhibitor with IC50 of 5 nM. It has no relevant inhibition of any of the other tested proteins at 100 μM, although TH588 showed reasonable selectivity when tested on a much larger panel of 87 enzymes, GPCRs, kinases, ion channels and transporters at 10 μM.
in vitro	TH588 selectively kill U2OS and other cancer cell lines with less toxic to several primary or immortalized cells. TH588 also induces DNA damage and triggers an ATM-p53-mediated death response and DNA repair in U2OS cells. ^[1]
in vivo	In mice bearing SW480 colorectal or MCF7 breast tumor xenografts, TH588 (30 mg/kg s.c.) reduces tumor growth via MTH1 inhibition. In mice carrying patient with BRAFV600E mutated xenografts, TH588 (30 mg/kg s.c.) also causes a reduced tumor growth rate. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	IC50 value determination
キナーゼアッセイ	The compounds to be analyzed are first serially diluted in DMSO in a 1:3 dilution series and then further diluted in assay buffer (100 mM Tris-acetate, 40 mM NaCl, 10 mM Mg acetate, 1 mM DTT and 0.005% Tween 20) generating 11 different compound concentrations giving a final DMSO concentration of 1% in the assay well. MTH1 is added to a final concentration of 4.8 nM. dGTP is added to a final concentration of 100 μM and 0.2 U/mL inorganic pyrophosphatase is added to a final volume of 100 μL. A dilution series of a QC substance is included on each assay plate as well as controls lacking enzyme (negative control) or inhibitor (positive control). The reaction mixture is incubated with shaking for 15 min at 22 °C. 25 μL malachite green assay reagent is added followed by incubation with shaking for 15 min at 22 °C. The absorbance of the assay plate is read at 630 nm using an EnVision Multilabel plate reader. The IC50 value is determined by fitting a dose response curve to the data points using nonlinear regression analysis.
動物実験	動物モデル	SCID mice bearing SW480 xenografts or MCF-7 xenografts; NOD-SCID IL2Rγ^null (NOG) mice bearing patient with BRAFV600E mutated xenografts
	投薬量	30 mg/kg, once daily
	投与方法	s.c.

参考

[1] Gad H, et al. Nature. 2014, 508(7495), 215-221.

カスタマーフィードバック

: Data from [Data independently produced by , , Anal Chim Acta, 2016, 905:66-71.]

: Data from [Data independently produced by , , Oncol Lett, 2018, 15(3):3240-3244]

: Data from [Data independently produced by , , Oncol Lett, 2017, 13(4):2161-2168]

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：

Platinum-based nanocomposites loaded with MTH1 inhibitor amplify oxidative damage for cancer therapy [ Colloids Surf B Biointerfaces, 2022, 218:112715]	PubMed: 35932557
VISAGE Reveals a Targetable Mitotic Spindle Vulnerability in Cancer Cells. [ Cell Syst, 2019, 9(1):74-92.e8]	PubMed: 31302152
TH588, an MTH1 inhibitor, enhances phenethyl isothiocyanate-induced growth inhibition in pancreatic cancer cells [Ikejiri F, et al. Oncol Lett, 2018, 15(3):3240-3244]	PubMed: 29435064
Modification of tumour cell metabolism modulates sensitivity to Chk1 inhibitor-induced DNA damage. [Massey AJ Sci Rep, 2017, 7:40778]	PubMed: 28106079
Expression and function of MutT homolog 1 in distinct subtypes of breast cancer. [Zhang X, et al. Oncol Lett, 2017, 13(4):2161-2168]	PubMed: 28454376
Investigation of MTH1 activity via mismatch-based DNA chain elongation [Gao T, et al. Anal Chim Acta, 2016, 905:66-71]	PubMed: 26755138

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。