title: Development and validation of a 96-well cellular assay for the discovery of ALDH1A1 inhibitors.
abstract: Retinoic acid, the active metabolite of vitamin A, plays important roles in various physiological and pathological processes. The two-step production of retinoic acid from vitamin A (retinol) is catalyzed by alcohol dehydrogenases and aldehyde dehydrogenases, which are potential therapeutic targets for numerous diseases, such as obesity, diabetes, and cancer. Currently, the lack of a suitable high-throughput cellular assay hinders efforts to identify therapeutic small molecular inhibitors of aldehyde dehydrogenase, such as ALDH1A1. In this report, we utilized high-content imaging technology and a commercially available cell permeable ALDH substrate to develop a 96-well cellular ALDH1A1 assay. This assay has a robust and sensitive readout and is amenable to automation. With this cellular assay, we identified potent selective ALDH1A1 inhibitors to explore the role of retinoic acid production in various preclinical disease models.
authors: Endocrine and Cardiovascular Research Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA.
authors: Wenyu
authors: W
authors: Ming
authors: Wenzhen
authors: W
authors: Ma
authors: Lisa H
authors: LH
authors: Chen
authors: Catherine
authors: C
authors: Volk
authors: Mervyn Dodson
authors: MD
authors: Michael
authors: Yanping
authors: Y
authors: Xu
authors: Fang
authors: F
authors: Zhang
authors: Xiaojun
authors: X
authors: Wang
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D001896:Boron Compounds / Q000378:metabolism; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000032:analysis*; D056945:Hep G2 Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D011933:Reagent Kits, Diagnostic; D050697:Retinal Dehydrogenase
chemical_list: C120929:BODIPY acetoacetaldehyde; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D011933:Reagent Kits, Diagnostic; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase