AI26 inhibits the ADP-ribosylhydrolase ARH3 and suppresses DNA damage repair.

ABSTRACT: The ADP-ribosylhydrolase ARH3 plays a key role in DNA damage repair, digesting poly(ADP-ribose) and removing ADP-ribose from serine residues of the substrates. Specific inhibitors that selectively target ARH3 would be a useful tool to examine DNA damage repair, as well as a possible strategy for tumor suppression. However, efforts to date have not identified any suitable compounds. Here, we used in silico and biochemistry screening to search for ARH3 inhibitors. We discovered a small molecule compound named ARH3 inhibitor 26 (AI26) as, to our knowledge, the first ARH3 inhibitor. AI26 binds to the catalytic pocket of ARH3 and inhibits the enzymatic activity of ARH3 with an estimated IC₅₀ of ∼2.41 μm in vitro Moreover, hydrolysis of DNA damage-induced ADP-ribosylatio

SUBMITTER: Liu X 

PROVIDER: S-EPMC7535916 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature