ARQ761

ARQ761 is a clinical-stage small molecule formulation of beta-lapachone, a naturally occurring quinone being developed for the treatment of NQO1-overexpressing solid tumors and lymphomas. The drug acts as a pro-drug that is specifically bioactivated by the enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), which is highly expressed in approximately 90% of pancreatic cancers and significantly elevated in other solid malignancies such as breast and non-small cell lung cancer. Upon bioactivation, ARQ761 initiates a futile redox cycle that generates massive amounts of reactive oxygen species (ROS), leading to extensive DNA damage. This damage hyperactivates Poly(ADP-ribose) polymerase 1 (PARP1), causing a catastrophic depletion of cellular NAD+ and ATP pools, ultimately resulting in a unique form of programmed necrosis known as NAD+-keresis. ARQ761 is being developed by the University of Texas Southwestern Medical Center in collaboration with NQ Oncology and Merck (following the acquisition of ArQule), and is frequently investigated in combination with PARP inhibitors to exploit synthetic lethality.

Brand names

Mazence

Other names

beta-lapachonebeta lapachoneB-lapachone