| Identification | Back Directory | [Name]
TH588 | [CAS]
1609960-31-7 | [Synonyms]
TH588
CS-1701
TH588, >98%
TH588(TH-588)
TH 588;TH-588;TH588
N4-cyclopropyl-6-(2,3-dic
6-(2,3-dichlorophenyl)-N4-cyclopropylpyrimidine-2,4-diamine
N4-cyclopropyl-6-(2,3-dichlorophenyl)pyrimidine-2,4-diamine
N4-Cyclopropyl-6-(2,3-dichlorophenyl)-2,4-pyrimidinediamine
2,4-Pyrimidinediamine, N4-cyclopropyl-6-(2,3-dichlorophenyl)- | [Molecular Formula]
C13H12Cl2N4 | [MDL Number]
MFCD28963908 | [MOL File]
1609960-31-7.mol | [Molecular Weight]
295.17 |
| Chemical Properties | Back Directory | [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. |
| Hazard Information | Back Directory | [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. | [in vivo]
TH588 (30 mg/kg; s.c.; once daily for 35 days) reduces tumour growth in SW480 xenograft cancer model[1]. | Animal Model: | 5-6 weeks female SCID mice (SW480 xenograft cancer model)[1] | | Dosage: | 30 mg/kg | | Administration: | Subcutaneous injection; once daily for 35 days | | Result: | Reduced tumour growth in SW480 xenograft cancer model. |
| [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 |
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