Structural studies of aldo-keto reductase inhibition.

Abstract

Aldose reductase (ALR2) has long been a target for drug design to combat complications which arise in diabetes (Dvornik et al., 1973). The enzyme’s ability to reduce in an NADPH-dependent manner, glucose in its carbonyl-containing, open chain form to sorbitol has been linked to a number of these complications affecting a number of tissues. A large number of ALR2 inhibitors have been developed (reviewed in Sarges & Oates, 1993) but most have not proven to be clinically effective. These disappointing results may be attributed to the inhibition of other members of the aldo-keto reductase family of proteins. This set of enzymes shares considerable sequence homology and consequently has overlapping substrate and inhibitor specificity.KeywordsAldose ReductaseAldose Reductase InhibitorNicotinamide RingInhibitor Binding SiteOpen Chain FormThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.