LFHP-1c

LFHP-1c is a novel small molecule inhibitor targeting the mitochondrial phosphatase PGAM5. It demonstrates neuroprotective properties in preclinical models of ischemic stroke by protecting blood-brain barrier (BBB) integrity and shows efficacy in reducing cerebral infarct size, brain edema, and neurological deficits following ischemic injury in rodents and nonhuman primates. Mechanistically, LFHP-1c binds endothelial PGAM5, inhibits its phosphatase activity, and disrupts PGAM5-NRF2 interaction, thus facilitating NRF2 nuclear translocation and enhancing antioxidant defense. LFHP-1c also shows activity in models of vascular dementia and hepatocellular carcinoma, though anti-tumor effects may be independent of PGAM5. There is no evidence of approval or clinical trial use in humans; it is for preclinical research only[1][2][3][4][5][6][7][9][10].