Pharmacologic characterization of fluzoparib, a novel poly(ADP-ribose) polymerase inhibitor undergoing clinical trials.

ABSTRACT: Poly(ADP-ribose) polymerase (PARP) enzymes play an important role in repairing DNA damage and maintaining genomic stability. Olaparib, the first-in-class PARP inhibitor, has shown remarkable clinical benefits in the treatment of BRCA-mutated ovarian or breast cancer. However, the undesirable hematological toxicity and pharmacokinetic properties of olaparib limit its clinical application. Here, we report the first preclinical characterization of fluzoparib (code name: SHR-3162), a novel, potent, and orally available inhibitor of PARP. Fluzoparib potently inhibited PARP1 enzyme activity and induced DNA double-strand breaks, G₂ /M arrest, and apoptosis in homologous recombination repair (HR)-deficient cells. Fluzoparib preferentially inhibited the proliferation of HR-deficient cell

SUBMITTER: Wang L 

PROVIDER: S-EPMC6398880 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature