Tolrestat is a potent, orally active aldose reductase inhibitor with IC50 of 35 nM. IC50: 35 nM (Aldose Reductase)
Tolrestat (1.8 mg/kg per day) causes a reversal to normal RBC sorbitol levels diabetic rats[1]. In 21-day diabetic rats, the estimated ID in the sciatic nerve and lenses is 4.8 and about 20 for tolrestat, and 1.7 and 2.2 for (±)sorbinil,respectively[2]. Either tolrestat or sorbinil inhibits tissue AR activity but does not significantly affect plasma lipoprotein levels, or affect the body weight of the mice or their general health. Accumulation of cholesterol-rich foam cells is significantly increased in aortic roots of tolrestat-fed mice[3].
[1]. Sestanj K, et al. N-[5-(trifluoromethyl)-6-methoxy-1-naphthalenyl]thioxomethyl]- N-methylglycine (Tolrestat), a potent, orally active aldose reductase inhibitor. J Med Chem. 1984 Mar;27(3):255-6. [2]. Simard-Duquesne N, et al. The effects of a new aldose reductase inhibitor (tolrestat) in galactosemic and diabetic rats. Metabolism. 1985 Oct;34(10):885-92. [3]. Srivastava S, et al. Aldose reductase protects against early atherosclerotic lesion formation in apolipoprotein E-null mice. Circ Res. 2009 Oct 9;105(8):793-802.