POMHEX

POMHEX is a lipophilic bis-ester prodrug of HEX (also known as SF2312 or 1-hydroxy-2-oxopiperidin-3-yl phosphonate), a small molecule phosphonate inhibitor of enolase 2 (ENO2). Developed by researchers at the University of Texas MD Anderson Cancer Center, POMHEX is designed to exploit the concept of "collateral lethality" in cancers characterized by the homozygous deletion of the enolase 1 (ENO1) gene, such as glioblastoma, hepatocellular carcinoma, and cholangiocarcinoma. Because ENO1 and ENO2 are redundant paralogs in the glycolytic pathway, cells lacking ENO1 become uniquely dependent on ENO2 for survival. POMHEX is bioactivated by intracellular esterases to release the active inhibitor HEX, which competitively binds to the ENO2 active site. Preclinical studies have demonstrated its efficacy in inducing tumor regression in ENO1-deleted intracranial xenograft models, although its development has also led to the exploration of second-generation prodrugs with improved pharmacokinetic stability.

Other names

bis(pivaloyloxymethyl) (1-hydroxy-2-oxopiperidin-3-yl)phosphonate