ARI-809

ARI-809 (CP-744809) is a highly selective, orally active aldose reductase inhibitor with an IC₅₀ of 1 nM. ARI-809 blocks excessive glucose flux through the polyol pathway. ARI-809 normalizes elevated sorbitol and fructose levels in sciatic nerve tissues of diabetic rat models, inhibits sorbitol accumulation in lens tissues, and brings elevated urinary albumin excretion close to normal. ARI-809 can be used in diabetes research^[1]. In Vitro:ARI-809 (CP-744809) shows high selectivity for aldose reductase over related dehydrogenases, with the lowest off-target potency against aldehyde reductase (IC₅₀ = 930 nM) and minimal activity against alcohol, fructose, and sorbitol dehydrogenases^[1]. In Vivo:ARI-809 (0.2-4.0 mg/kg; oral gavage; single doses at 4,7,24h post-streptozotocin (acute); once daily for 5 days (chronic)) potently normalizes elevated polyol pathway metabolites in diabetic rat sciatic nerve and lens tissues, with ED₅₀ values of 0.2 mg/kg and 0.8 mg/kg for sorbitol and fructose normalization in the acute test, and ED₉₀ values of 0.8 mg/kg and 4.0 mg/kg for sorbitol and fructose normalization in the chronic test, while also reducing urinary albumin output in diabetic rats^[1].