TH287 is a potent MTH1 inhibitor with IC50 of 0.8±0.1 nM. [1]
MTH1 (human MutT homolog 1) is an antimutagenic purine nucleoside triphosphatase that sanitize oxidized nucleotide pools. It’s a new cancer therapeutic target as it protects the cancer cell from DNA damages such as oxidative stress-induced cell dysfunction or death.
In U2OS and other cancer cell lines, TH287 treatment selectively and effectively kill cancer cells with less toxic to some primary or immortalized cells. U2OS cells treated with TH287 shows increase of 8-oxodG in DNA. The MTH1 inhibitor TH287 induces DNA damage and activates an ATM-p53-mediated death response and DNA repair in U2OS cells. [1]
Reference:
1. Gad H, Koolmeister T, Jemth AS et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature. 2014 Apr 10;508(7495):215-21.