A selective inhibitor of the nucleotide pool sanitizing enzyme MTH1 (IC50 = 5 nM) that kills cancer cell lines (IC50s = 2.48-6.37 µM); reduces tumor growth in mouse xenografts

TH588 – 1 mg

Brand:
Cayman
CAS:
1609960-31-7
Storage:
-20
UN-No:
Non-Hazardous - /

Human mutT homolog (MTH1) is a nucleotide pool sanitizing enzyme that cleaves oxidized nucleotides (dNTPs) to prevent incorporation of damaged bases during DNA replication. Cancer cells rely on MTH1 activity in order to avoid cell death. TH588 is an MTH1 inhibitor (IC50 = 5 nM) with improved metabolic stability over TH287 (Item No. 18132).{29777} It selectively kills cancer cell lines (IC50s = 2.48-6.37 µM) without significant cytotoxicity towards primary or immortalized cells (IC50s = ≥20 µM) and demonstrates >1,000-fold selectivity for MTH1 over the related nudix hydrolase protein family members MTH2, NUDT5, NUDT12, NUDT14, and NUDT16, as well as other proteins with known nucleoside triphosphate pyrophosphatase activity (dCTPase, dUTPase, and ITPA).{29777} At 30 mg/kg, TH588 induces incorporation of oxidized dNTPs in cancer cells, leading to DNA damage and cell death in B-RafV600E melanoma, SW480 colorectal, or MCF-7 breast tumor mouse xenografts.{29777}  

 

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Description

A selective inhibitor of the nucleotide pool sanitizing enzyme MTH1 (IC50 = 5 nM) that kills cancer cell lines (IC50s = 2.48-6.37 µM); reduces tumor growth in mouse xenografts

Formal name: N4-cyclopropyl-6-(2,3-dichlorophenyl)-2,4-pyrimidinediamine

Synonyms: 

Molecular weight: 295.2

CAS: 1609960-31-7

Purity: ≥98%

Formulation: A crystalline solid

Product Type|Biochemicals|Small Molecule Inhibitors|Nucleic Acid Turnover/Signaling||Research Area|Cancer|Cell Death||Research Area|Cancer|DNA Damage and Repair

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