TH588

• CAT Number: I002051
• CAS Number: 1609960-31-7
• Molecular Formula: C13H12Cl2N4
• Molecular Weight: 295.2
• Purity: ≥95%
• Target: MTH1
• Solubility: DMSO: ≥ 16 mg/mL
• Storage: Store at -20°C
• IC50: 5 nM [1]
• 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)
• InChIKey: PNMYJIOQIAEYQL-UHFFFAOYSA-N
• SMILES: NC1=NC(NC2CC2)=CC(C3=CC=CC(Cl)=C3Cl)=N1

TH588 (CAT: I002051) is a first-in-class inhibitor of the nudix hydrolase family, specifically targeting the enzyme MTH1 (MutT Homolog 1). MTH1 is involved in the prevention of the incorporation of oxidized nucleotides into DNA during replication. By selectively inhibiting MTH1, TH588 disrupts the cellular defense against oxidative damage, leading to the accumulation of oxidized nucleotides in DNA and subsequent DNA damage. TH588 has demonstrated potent inhibitory activity against MTH1 in cellular assays, with an IC50 value of 5 nM.

Reference

1:Reactive Oxygen Species Dictate the Apoptotic Response of Melanoma Cells to TH588. Wang JY, Jin L, Yan XG, Sherwin S, Farrelly M, Zhang YY, Liu F, Wang CY, Guo ST, Yari H, La T, McFarlane J, Lei FX, Tabatabaee H, Chen JZ, Croft A, Jiang CC, Zhang XD.J Invest Dermatol. 2016 Nov;136(11):2277-2286. doi: 10.1016/j.jid.2016.06.625. Epub 2016 Jul 15. PMID: 27427486 Free Article2:Development and validation of method for TH588 and TH287, potent MTH1 inhibitors and new anti-cancer agents, for pharmacokinetic studies in mice plasma. Saleh A, Gökturk C, Warpman-Berglund U, Helleday T, Granelli I.J Pharm Biomed Anal. 2015 Feb;104:1-11. doi: 10.1016/j.jpba.2014.11.009. Epub 2014 Nov 15. PMID: 25459754