ART558 (ART-558) is a highly potent, selective, allosteric inhibitor of the polymerase function of DNA polymerase Polθ with IC50 of 7.9 nM.
ART558 does not inhibit other human DNA polymerases, namely Polα, Polγ, Polη and Polν, as well as a panel of 78 oncology-focussed kinases, including PARP1 and PARP2.
ART558 inhibits the major Polθ-mediated DNA repair process, Theta-Mediated End Joining, without targeting Non-Homologous End Joining (NHEJ).
ART558 elicits DNA damage and synthetic lethality in BRCA1- or BRCA2-mutant tumour cells and enhances the effects of PARP inhibitor Olaparib.
