HA344 (HA 344) is a dual covalent inhibitor of pyruvate kinase M2 (PKM2) and inosine monophosphate dehydrogenase (IMPDH), efficiently inhibits cutaneous metastatic melanoma (CMM).
HA344 inhibits glycolysis and purine metabolism and induces cell death that is rescued by pyruvate in CMM cell lines.
HA344 directly inhibits PKM glycolytic enzymatic activity with IC50 of 1 uM in vitro, mutant PKM2 C424L is no longer inhibited by HA344.
HA344 efficiently targeted vemurafenib-sensitive and vemurafenib-resistant CMM cells.
HA344 (5 mg/kg/day) reduced tumor growth in mice xenografted with CMM.
