3G5E

Human aldose reductase complexed with IDD 740 inhibitor

Summary for 3G5E

• Entry DOI: 10.2210/pdb3g5e/pdb
• Related: 1Z3N
• Descriptor: Aldose reductase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-(3-((4,5,7-trifluorobenzo[d]thiazol-2-yl)methyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)acetic acid, ... (4 entities in total)
• Functional Keywords: aldose reductase, inhibition, diabetes, acetylation, cataract, cytoplasm, nadp, oxidoreductase, phosphoprotein, polymorphism
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37303.38

Authors

Podjarny, A.D.,Van Zandt, M.C. (deposition date: 2009-02-05, release date: 2009-03-24, Last modification date: 2024-03-20)

Primary citation

Van Zandt, M.C.,Doan, B.,Sawicki, D.R.,Sredy, J.,Podjarny, A.D.
Discovery of [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]acetic acids as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.
Bioorg.Med.Chem.Lett., 19:2006-2008, 2009

PubMed Abstract: Efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective [3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]acetic acid aldose reductase inhibitors. The lead candidate, [6-methyl-3-(4,5,7-trifluoro-benzothiazol-2-ylmethyl)-pyrrolo[2,3-b]pyridin-1-yl]acetic acid example 16, inhibits aldose reductase with an IC50 of 8 nM, while being inactive against aldehyde reductase (IC50>100 microM), a related enzyme involved in the detoxification of reactive aldehydes.

PubMed: 19250825
DOI: 10.1016/j.bmcl.2009.02.037

Experimental method

X-RAY DIFFRACTION (1.8 Å)