4QX4

Human Aldose Reductase complexed with a ligand with a new scaffold at 1.26 A

Summary for 4QX4

• Entry DOI: 10.2210/pdb4qx4/pdb
• Related: 1US0
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, (3-thioxo-2,3-dihydro-5H-[1,2,4]triazino[5,6-b]indol-5-yl)acetic acid, ... (4 entities in total)
• Functional Keywords: tim barrel, oxidoreductase, oxidoreductase-oxidoreductase inhibitor complex, oxidoreductase/oxidoreductase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37162.29

Authors

Rechlin, C.,Heine, A.,Klebe, G. (deposition date: 2014-07-18, release date: 2015-04-01, Last modification date: 2023-09-20)

Primary citation

Stefek, M.,Soltesova Prnova, M.,Majekova, M.,Rechlin, C.,Heine, A.,Klebe, G.
Identification of novel aldose reductase inhibitors based on carboxymethylated mercaptotriazinoindole scaffold.
J.Med.Chem., 58:2649-2657, 2015

PubMed Abstract: Fifteen compounds, sharing an indole-1-acetic acid moiety as a common fragment, were selected from commercial databases for testing aldose reductase inhibition. 3-Mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (13) was the most promising inhibitor, with an IC50 in the submicromolar range and high selectivity, relative to aldehyde reductase. The crystal structure of aldose reductase complexed with 13 revealed an interaction pattern explaining its high affinity. Physicochemical parameters underline the excellent "leadlikeness" of 13 as a promising candidate for further structure optimizations.

PubMed: 25695864
DOI: 10.1021/jm5015814

Experimental method

X-RAY DIFFRACTION (1.259 Å)