Discovery of novel anti-tumor compounds targeting PARP-1 with induction of autophagy through in silico and in vitro screening.

ABSTRACT: Poly (ADP-ribose) polymerase 1 (PARP-1) is a critical enzyme involved in DNA damage repair and recombination, and shows great potential for drug development in the treatment of cancers with defective DNA repair. The anti-tumor activities of PARP-1 inhibitors are regulated by both inhibition activities and allosteric mechanisms of PARP-1, and may also be involved in an autophagy-mediated process. Screening PARP-1 inhibitors with potential allosteric mechanisms and induced autophagy process could achieve elevated potency toward cancer cell killing. In this study, we tried to discover novel anti-tumor compounds targeting PARP-1 by computer simulations and in vitro screening. In order to filter PARP-1 inhibitors that could affect the folding state of the helix domain (HD) on PARP-1, the

SUBMITTER: Shi D 

PROVIDER: S-EPMC9638114 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature