1609960-31-7|TH588(TH588)|CsnPharm

CAS No.: 1609960-31-7

TH588 Catalog No. CSN13872

Synonyms: TH588

TH588 is a potent human MTH1 (NUDT1) inhibitor with an IC50 value of 5 nM.

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生物活性

实验方案

技术信息

生物活性

描述The nucleotide-sanitizing enzyme MutT homolog 1 (MTH1) efficiently hydrolyzes oxidized nucleoside triphosphates to nucleoside monophosphates. TH588 is a first-in-class nudix hydrolase family inhibitors that potently and selectively inhibit the MTH1 protein in cells with an IC50 value of 5nM and causes incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses. TH588 effectively reduced cellular survival in heterogeneous neuroendocrine tumor cells (pancreatic BON1, pancreatic islet QGP1, bronchopulmonary H727 and ileal GOT1) in a time- and dose- dependent manner (IC20 ranging in 1.5 - 8.2 uM) and also decreased phosphorylation of Akt and 4EBP1 compared with controls. Daily TH588 subcutaneous treatment (30 mg/kg) caused 92.7% and 90.4% regression of breast cancer cells MCF7 and MDA-MB-23 xenografts respectively, compared with model group.
作用机制TH588 inhibits MTH1 by forming hydrogen bonds with Phe72 and Met81 and π-π stacking with Phe72.
动物研究
剂量
Mice: 30 mg/kg^[2] (s.c.)

给药途径
s.c.

动物药代数据
Animal Mice^[2]
Dose 25 mg/kg
Administration s.c.
AUC_0→inf 337 μmol·h/ml
T_1/2z 4.8 h
T_max 2 h
C_max 35 M
AUC_0→t 195 μmol·h/ml
参考文献

[1] Aristizabal Prada ET, Orth M, et al. The MTH1 inhibitor TH588 demonstrates anti-tumoral effects alone and in combination with everolimus, 5-FU and gamma-irradiation in neuroendocrine tumor cells. PLoS One. 2017 May 25;12(5):e0178375.
[2] Gad H, Koolmeister T, et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014 Apr 10;508(7495):215-21.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 3.3879 mL
- 16.9396 mL
- 33.8791 mL
- 5 mM
- 0.6776 mL
- 3.3879 mL
- 6.7758 mL
- 10 mM
- 0.3388 mL
- 1.6940 mL
- 3.3879 mL

技术信息

CAS号

1609960-31-7

储存条件

粉末: Keep in dark place,Inert atmosphere,Room temperature

液体: -20°C:3-6 月 -80°C:12月

分子式

C13H12Cl2N4

运输

蓝冰

分子量

295.17

别名

TH588

溶解度

DMSO	25.0 mg/mL (84.7 mM)
Water	insoluble

动物实验配方

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