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zenarestat
- Development stage
- Discontinued
- Lead developer
- Astellas Pharma
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Zenarestat is a small molecule aldose reductase inhibitor that was investigated for the treatment of diabetic neuropathy and cataract. Its mechanism of action involves inhibition of aldose reductase (AKR1B1), the first enzyme in the polyol pathway, thereby reducing sorbitol accumulation in tissues such as nerves, retina, lens, and renal cortex. By suppressing this pathway, zenarestat aimed to prevent or slow the progression of diabetic complications like polyneuropathy by mitigating hyperglycemia-induced cellular damage. Zenarestat demonstrated high specificity for aldose reductase over related enzymes and showed efficacy in preclinical models and clinical trials by improving nerve conduction velocity and reducing nerve fiber loss. However, its development was discontinued due to dose-dependent renal toxicity[1][2][3][6][7].
- Other names
- zenarestat
02
Targets
AR (Adrenergic receptors)
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