POMHEX, a racemic mixture and a cell-permeable pivaloyloxymethyl (POM) prodrug of HEX, is a potent, ENO2-specific inhibitor of enolase. POMHEX exhibits low-nanomolar potency against ENO1-deleted cells in vitro and is capable of eradicating ENO1-deleted xenografted tumours in vivo. POMHEX is a potent glycolysis inhibitor.In Vitro:POMHEX (78 nM, 8h) minimally impacts ENO1-WT glioma cells but profoundly affected ENO1-deleted cells.
POMHEX (0-720 nM) selectively induces energy stress, inhibits proliferation and triggers apoptosis in ENO1-deleted glioma cells.
In Vivo:POMHEX (i.v., ip) injections are consistently tolerated without haemolytic anaemia at doses of up to 10 mg per kg (body weight) per day. POMHEX (i.v., 35 mg/kg) results in lethargy that prompted veterinarians to perform euthanasia.
POMHEX is rapidly hydrolysed to HemiPOMHEX in mouse plasma ex vivo, with a half-life of approximately 30 s, the half-life in human blood ex vivo was about 9min.