Ranirestat (AS-3201) potent and orally active aldose reductase (AR) inhibitor with IC₅₀s of 11 nM and 15 nM for rat lens AR and recombinant human AR, respectively, and a K_i of 0.38 nM for recombinant human AR. Ranirestat has the potential for diabetic sensorimotor polyneuropathy treatment. Ranirestat also has a neuroprotective effect on diabetic retinas^[1][2]. IC50 & Target: IC50: 11 nM (Rat lens aldose reductase) and 15 nM (Recombinant humanaldose reductase)^[1]
Ki: 0.38 nM (Recombinant humanaldose reductase)^[1] In Vitro: Ranirestat concentration-dependently inhibits sorbitol accumulation in rat erythrocytes and sciatic nerves incubated in the high concentration (500 mg/dl) of glucose. The potency of Ranirestat inhibition of sorbitol accumulation is similar between rat erythrocytes and sciatic nerves with IC₅₀ values of 0.010 μM and 0.041 μM, respectively^[1]. In Vivo: Ranirestat (0.03-1.0 mg/kg; oral administration; once daily; for 3 weeks; male STD-Wistar rats) treatment dose-dependently decreases the elevated sorbitol and fructose levels in the rat sciatic nerves without affecting blood glucose level. Ranirestat also improves the STZ-induced decrease in motor nerve conduction velocity (MNCV) in a dose-dependent manner^[1].