PARP1-IN-10 (compound 12c) is a highly potent and non-cytotoxic PARP1 inhibitor, displaying an in vitro IC50 value of 50.62 nM. This compound effectively induces cell cycle arrest at the G2/M phase and apoptosis, while also significantly augmenting the cytotoxic effects of temozolomide (TMZ) [1].

PARP1-IN-10 (compound 12c) demonstrated no cytotoxicity at a concentration of 10 μM over 48 hours against NCI-60 human tumor cell lines. It effectively inhibited the MDA-MB-436 cell line, presenting an IC50 value of 3.73 μM. Furthermore, administration of PARP1-IN-10 at concentrations of 1 and 3.73 μM for 48 hours induced cell cycle arrest at the G2/M phase in a dose-dependent manner. Additionally, at a lower dose of 0.5 μM for 48 hours, PARP1-IN-10 significantly enhanced the anti-proliferative effect of temozolomide (TMZ) in A549 cell lines, making it approximately 7 times more effective than TMZ alone (reducing the IC50 from 24.2 μM to 3.64 μM). These results, encompassing cytotoxicity assays, cell cycle, and apoptosis analysis, underline the potential of PARP1-IN-10 as a therapeutic agent, specific in its action and synergistic with existing treatments like TMZ.