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| 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 | | EINECS: | | 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. | | 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 |
| TH588 Preparation Products And Raw materials |
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