PARP1 inhibitor (selective)

Selective PARP1 inhibitors are a next-generation class of small molecule therapeutics designed to target poly(ADP-ribose) polymerase 1 (PARP1) while sparing PARP2. First-generation PARP inhibitors (such as olaparib, niraparib, rucaparib, and talazoparib) are dual PARP1/2 inhibitors. While highly effective in homologous recombination-deficient (HRD) cancers (such as those with BRCA1/2 mutations) through synthetic lethality, their clinical utility is limited by hematological toxicities (such as anemia and thrombocytopenia) driven primarily by PARP2 inhibition. By selectively targeting PARP1, these next-generation inhibitors aim to significantly improve the therapeutic index, reduce hematotoxicity, and enable combination therapies with standard-of-care chemotherapies, radiotherapies, or other targeted agents. Several selective PARP1 inhibitors, including AstraZeneca's saruparib (AZD5305) and Duke Street Bio's DSB2455, are currently in clinical development for various solid tumors, including breast, ovarian, prostate, and pancreatic cancers, as well as brain metastases.

Other names

PARP1 selective inhibitorPARP-1 selective inhibitorPARP 1 selective inhibitorPARP1-selective inhibitorPARP-1-selective inhibitorPARP 1-selective inhibitorselective PARP1 inhibitor