bs-60211C

DATASHEET

Formulation Powder

Storage: Store in dry, dark place at -20C for 1 year.

Product Information:

Molecular Weight: 295.17

Formula: C13 H12 Cl2 N4

CAS Number: 1609960-31-7

InChi Key: PNMYJIOQIAEYQL-UHFFFAOYSA-N

InChi: InChI=1S/C13H12Cl2N4/c14-9-3-1-2-8(12(9)15)10-6-11(17-7-4-5-7)19-13(16)18-10/h1-3,6-7H,4-5H2,(H3,16,17,18,19)

Smiles: NC1N=C(C=C(N=1)C1C=CC=C(Cl)C=1Cl)NC1CC1

Purity: 98.0

Solubility: DMSO up to 50 mM

Appearance: Solid Power

Shelf Life: 1.0 years

Description:

TH588 is a novel potent, selective and cell permeable inhibitor of the nudix hydrolase family MTH1 protein with an IC50 of ~5 nM. Protein co-crystal structures demonstrate that TH588 binds in the active site of MTH1. It has excellent selectivity over other nudix family proteins and kinases present in the selectivity panel. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, the cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs. MTH1 inhibition by TH588 causes incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. TH588 is a good chemical tool to exemplify the non-oncogene addiction concept for anticancer treatment and validate MTH1 as a drug target.