TH1760

TH1760 is an inhibitor of NUDIX-type 15 (NUDT15) with an IC50 value of 25 nM. TH1760 sensitizes cells to 6-thioguanine by enhancing the accumulation of 6-thio- (d) GTP in nucleic acids. TH1760 enhances the anti-leukemia effect of thiopurine[1][2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

NUDIX-type 15, NUDT15[1]

TH1760 (0-100 µM) 以剂量依赖的方式维持了 NUDT15 的热变性[1]。 TH1760 (0、5、10、20 和 50 µM) 以剂量依赖的方式增加了硫基嘌呤 (6-TG) 的积累[1]。 TH1760 (10 µM) 增加了 HCT116 和 HCT116 3-6 细胞对 6-TG 的敏感性。TH1760 对 BJ-RAS 细胞致敏性更高相比于 BJ-hTERT 细胞[1]。 TH1760 (10 µM；16 h) 促进 6-TG 在 HL-60 细胞中的积累与掺入。TH1760 增加了 HL-60 细胞中 γH2AX、caspase3、Cleaved 和 cPARP 的表达[1]。 TH1760 (0.05、0.17、0.55 和 1.8 µM；4 d) 以剂量依赖的方式增强了 6-TG 的抗白血病作用[2]。 Western Blot Analysis[1] Cell Line: HCT116 cells. Concentration: 10 µM. Incubation Time: 4 h. Result: Inhibited the expression of NUDT15. Western Blot Analysis[2] Cell Line: AML HL-60 cells. Concentration: 10 µM. Incubation Time: 3 h. Result: Significantly inhibited the expression of NUDT15 when the temperature was higher than 54℃.

[1]. Zhang SM, et al. Development of a chemical probe against NUDT15. Nat Chem Biol. 2020 Oct;16(10):1120-1128.  

[2]. Rehling D, et al. Crystal structures of NUDT15 variants enabled by a potent inhibitor reveal the structural basis for thiopurine sensitivity. J Biol Chem. 2021 Jan-Jun;296:100568.