GS-9328

GS-9328 is a novel, potent, small-molecule inhibitor of ketohexokinase (KHK) developed by Gilead Sciences [FR-PO993]. Ketohexokinase is the primary and rate-limiting enzyme involved in fructose metabolism, converting fructose to fructose-1-phosphate. In proximal tubule cells, acute or chronic injury triggers endogenous fructose production via the polyol pathway and increases KHK activity, leading to ATP depletion, cell death, and inflammatory cascades [FR-PO993]. By inhibiting KHK, GS-9328 prevents ATP depletion and attenuates tubular injury, immune cell infiltration, and renal function decline [FR-PO993]. Preclinical studies in rodent models of ischemia/reperfusion injury and adenine-induced kidney injury have demonstrated its efficacy in reducing tubular damage and protecting against renal failure, supporting its potential development for acute and chronic kidney diseases [FR-PO993].