Basic information Safety Supplier Related

TH588

Basic information Safety Supplier Related

TH588 Basic information

Product Name:
TH588
Synonyms:
  • N4-Cyclopropyl-6-(2,3-dichlorophenyl)-2,4-pyrimidinediamine
  • TH588
  • N4-cyclopropyl-6-(2,3-dichlorophenyl)pyrimidine-2,4-diamine
  • TH588(TH-588)
  • 6-(2,3-dichlorophenyl)-N4-cyclopropylpyrimidine-2,4-diamine
  • TH 588;TH-588;TH588
  • CS-1701
  • TH588, >98%
CAS:
1609960-31-7
MF:
C13H12Cl2N4
MW:
295.17
Product Categories:
  • Inhibitors
Mol File:
1609960-31-7.mol
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TH588 Chemical Properties

Boiling point:
545.7±60.0 °C(Predicted)
Density 
1.505±0.06 g/cm3(Predicted)
storage temp. 
2-8°C
solubility 
Soluble in DMSO (up to 5 mg/ml).
form 
powder
pka
5.90±0.10(Predicted)
color 
white to light brown
Stability:
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
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Safety Information

WGK Germany 
3
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TH588 Usage And Synthesis

Description

TH588 (1609960-31-7) is a first-in-class nudix hydrolase family inhibitor.1?MTH1/NUDT1 is a family member that “sanitizes” oxidized deoxynucleotide triphosphates (dNTP) preventing their incorporation into DNA and thus avoiding DNA damage and cell death.? TH588 inhibits MTH1/NUDT1 (IC50?= 5 nM) leading to cell death in several cancer cell lines while not affecting normal cells.? Active?in vitro?and?in vivo.? Recent evidence has raised doubts about the cancer-killing ability of MTH1 inhibition.2,3?Conversely, TH588 has been also shown to decrease osteosarcoma cell viability, impair cell cycle, and increase apoptosis via an MTH1-dependent pathway.4

Uses

TH 588 acts as a novel potent and selective permeable inhibitor of the nudix hydrolase MTH1 protein. It acts as a good tool to show the non-oncogene addiction concept to anti-cancer treatments.

Biochem/physiol Actions

TH588 is a potent inhibitor of human 7,8-Dihydro-8-oxoguaninetriphosphatase MTH1 (NUDT1) with an IC50 value of 5 nM and good metabolic stability. MTH1 hydrolyzes oxidized purine nucleoside triphosphates that might otherwise be incorporated into DNA/RNA and contribute to DNA damage. MTH1 removal of oxidized nucleotides that result from increased levels of reactive oxygen species (ROS) in fast-proliferating cancer cells helps protect cancer cells from proliferative stress and prevent cancer cell death. TH588 is considered a new target for cancer therapy. TH588 is highly selective towards MTH1, with no relevant inhibition of other members of the nudix protein family or a panel of 87 enzymes, GPCRs, kinases, ion channels and transporter. TH588 has been shown to selectively kill a variety of cancer cell lines and with in vivo activity shown for TH588 in SW480 colorectal and MCF7 breast tumour xenografts.

storage

Store at -20°C

References

1) Gad?et al. (2014),?MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool; Nature,?508?215 2) Petrocchi et al. (2016)?Identification of potent and selective MTH1 inhibitors; Bioorg. Med. Chem. Lett.,?26?1503 3) Kettle?et al. (2016),?Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival; J. Med. Chem.,?59?2346 4) Moukengue?et al. (2020),?TH1579, MTH1 inhibitor, delays tumour growth and inhibits metastases development in osteosarcoma model; EBioMedicine,?53?102704

TH588Supplier

Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
Chembest Research Laboratories Limited
Tel
+86-21-20908456
Email
sales@BioChemBest.com
Dalian Meilun Biotech Co., Ltd.
Tel
0411-62910999 13889544652
Email
meilunui@163.com
Haoyuan Chemexpress Co., Ltd.
Tel
021-58950125
Email
info@chemexpress.com
Shanghai JiYi Biotechnology Co. Ltd.
Tel
13621943973
Email
sales@shjiyipharmatech.com