ARQ761 + olaparib

ARQ761 + olaparib is an investigational combination therapy consisting of ARQ761 (a clinical formulation of β-lapachone) and the PARP inhibitor olaparib. ARQ761 is a bioactivatable prodrug that targets NAD(P)H quinone dehydrogenase 1 (NQO1), an enzyme overexpressed in several cancers. Upon activation by NQO1, ARQ761 induces a futile redox cycle leading to excessive reactive oxygen species (ROS) production and DNA damage. Olaparib inhibits poly(ADP-ribose) polymerase 1/2 (PARP1/2), enzymes involved in DNA repair via the base excision repair pathway. The combination exploits synthetic lethality by increasing DNA damage through ROS while simultaneously blocking its repair with PARP inhibition, resulting in synergistic tumor-selective apoptosis—particularly in NQO1-overexpressing cancers such as non-small-cell lung cancer, pancreatic cancer, and breast cancer[1][2]. This approach aims to expand the efficacy of PARP inhibitors beyond BRCA-mutant tumors.

Other names

β-lapachone + olaparibbeta-lapachone + olaparibAZD2281 (for olaparib)KU-0059436 (for olaparib)