TH588
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
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.
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
- Tel
- sales@boylechem.com
- Tel
- +86-21-20908456
- sales@BioChemBest.com
- Tel
- 0411-62910999 13889544652
- meilunui@163.com
- Tel
- 021-58950125
- info@chemexpress.com
- Tel
- 13621943973
- sales@shjiyipharmatech.com
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