APO866

APO866, also known as FK866, is a small-molecule inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). NAMPT is the key enzyme in the NAD+ salvage pathway, converting nicotinamide to nicotinamide mononucleotide, a precursor of NAD+. By inhibiting NAMPT, APO866 depletes intracellular NAD+ pools, impairing energy metabolism and triggering cell death, with cancer cells generally showing greater sensitivity due to their higher metabolic demands.

In preclinical studies, APO866 demonstrated selective cytotoxicity toward cancer cells and showed potential in combination with other anticancer agents, such as DNA-damaging therapies and metabolic inhibitors. Clinically, APO866 has been evaluated in early-phase trials for a range of solid tumors and hematologic malignancies. While some patients exhibited antitumor activity, results have been variable, and dose-limiting toxicities, including fatigue and hematologic effects, have tempered enthusiasm. As a result, APO866 has not progressed to regulatory approval as a standalone therapy, and development efforts have mainly focused on combination strategies and identifying responsive patient populations.

APO866 is part of the broader class of NAMPT inhibitors, which target NAD+ biosynthesis to disrupt cellular energy production. Research continues into the therapeutic potential and limitations of NAMPT inhibition, including APO866, in oncology and related fields.