Aldo-Keto Reductase Family 1 Member B1 Inhibitors: Old Drugs with New Perspectives

Jianghua      Liu; Gebo      Wen; Deliang      Cao

doi:10.2174/157489209789206931

Abstract

Aldo-keto reductase 1 member B1 (AKR1B1) is pathogenically involved in diabetic complications by driving glucose flux through polyol pathway; a variety of AKR1B1 inhibitors has been developed for the treatment of diabetic complications and a body of invaluable preclinical and clinical data have been collected through decades efforts. Recent studies have shown that some AKR1B1 inhibitors demonstrate strong inhibitory activity to aldo-keto reductase family 1 member B10 (AKR1B10), a protein identical to AKR1B1, in vitro and in cancer cells. AKR1B1 and AKR1B10 are overexpressed in human tumors, such as liver, breast, and lung cancer, and may play a critical role in the development and progression of cancer through carbonyl detoxification, retinoic acid homeostatic regulation, and lipid metabolic control, as well as the activation of tobacco smoke carcinogens. Therefore, AKR1B1 inhibitors may represent a novel class of antitumor agents; and the clinical data assembled in diabetic clinics would greatly assist the transition of these inhibitors to cancer clinics. This article summaries the current understanding of the expression and function of AKR1B1 and AKR1B10 in human cancers and reviews the patents and papers of AKR1B1 inhibitors. Authors opinions concerning the current and future development of AKR1B1 and/or AKR1B10-specific inhibitors are discussed.

Keywords: Aldose reductase, aldose reductase-like-1, Aldo-keto reductase family 1 B1, Aldo-keto reductase family 1 B10, AR, ARL-1, AKR1B1, AKR1B10, aldose reductase inhibitor, ARI