Applied Therapeutics announced the initiation of a Phase 3 registrational trial for AT-001, a novel, potent and selective aldose
reductase inhibitor, in Diabetic Cardiomyopathy.
In tissues where glucose intake is independent of insulin, excess glucose is typically metabolized to sorbitol through the polyol pathway and this reaction is catalyzed by the aldose
The study, referred to as ACTION-Galactosemia, was initiated in June 2019and is designed to investigate the safety and pharmacokinetics (PK) of AT-007, a central nervous system (CNS) penetrant Aldose
Reductase (AR) inhibitor in healthy volunteers, and biomarker effects in adult subjects with Galactosemia.
reductase (AR) (EC 22.214.171.124) is expressed by the AKR1B1 gene in humans.
The enzyme aldose
reductase (AR) catalyses the reduction of glucose to sorbitol, but sorbitol is produced faster than it is converted to fructose meaning that it accumulates, creating a hyperosmotic effect that results in an infusion of fluid to counteract the osmotic gradient; this leads to the collapse and eventual liquefaction of lens fibres, which results in the lens becoming opaque.
Newer drugs called "aldose
reductase inhibitors" have been shown in a laboratory to delay or prevent cataract formation in diabetic dogs.
reductase inhibitory capacity of Sorbus domestica fruit extracts depends on their phenolic content and may be useful for the control of diabetic complications.
It has been hypothesized that swelling develops in the fluid content of peripheral nerves due to an increase in the levels of aldose
reductase enzyme, which converts glucose to sorbitol in patients with diabetes (3).
In addition, ranirestat, an inhibitor of the enzyme aldose
reductase, which has an early role in the development of DR , exerts neuroprotective effects by reducing GFAP accumulation and preventing hyperglycemia-associated structural damage of the retina .
Dasatinib is a dual Src/Abl  and pan-Src  kinase inhibitor, zopolrestat  and lidorestat  are aldose
reductase inhibitors used for the treatment of diabetic complications, and raloxifene is the first clinically available selective estrogen receptor modulator (SERM) used to prevent both osteoporosis and breast cancer [5-8].
Secondly, glucose may induce myoIns depletion by activation of the glucose-sorbitol pathway, in which glucose is first converted to sorbitol by aldose
reductase and then to fructose by sorbitol dehydrogenase, as observed in diabetic patients .
Reductase (AR) and Vasoproliferative Factors.