title: Evaluation of compound selectivity of aldo-keto reductases using differential scanning fluorimetry.
abstract: Inhibitors of AKR1B10 belonging to the aldo-keto reductase (AKR) superfamily are considered promising candidates for anti-cancer drugs. AKR1B1, a structurally similar isoform of AKR1B10, is involved in glucose metabolism. Thus, selective inhibition of AKR1B10 is required for the development of anti-cancer drugs. In this study, we first compared correlations between melting temperature and the 50% inhibition concentration obtained from differential scanning fluorimetry (DSF) and an enzyme inhibitory experiment, respectively, and a good correlation was found, except for compounds with low solubility. This result indicates that the DSF method is useful for drug screening for the AKR superfamily. We then evaluated their selectivity as inhibitors against all seven major human AKR1 family proteins and found that C18 is most specific for AKR1B10.
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Aurangazeb
authors.initials: A
authors.lastname: Kabir
authors.affiliation: Labolatory of Biochemistry, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi Gifu 501-1196, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.affiliation: Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Toyooka
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Fukuoka
authors.affiliation: United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.|Department of Gene and Development, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kuwata
authors.affiliation: Life Science Research Center, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Yuji O
authors.initials: YO
authors.lastname: Kamatari
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D057075:Enzyme Assays / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005470:Fluorometry / Q000379:methods*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010802:Phylogeny; D000072417:Protein Domains; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase
keywords: aldo-keto reductase; anti-cancer compound; compound selectivity; differential scanning fluorimetry; drug screening; thermal denaturation