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aldo-keto reductase family 1 member B

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Target id: 2768

Nomenclature: aldo-keto reductase family 1 member B

Family: 1.-.-.- Oxidoreductases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 316 7q33 AKR1B1 aldo-keto reductase family 1 member B
Mouse - 316 6 B1 Akr1b1 aldo-keto reductase family 1 member B
Rat - 316 4q22 Akr1b1 aldo-keto reductase family 1 member B1
Previous and Unofficial Names Click here for help
ALDR1 | AR | aldo-keto reductase family 1, member B1 (aldose reductase | aldo-keto reductase family 1, member B1 (aldose reductase) | aldo-keto reductase family 1 | aldo-keto reductase family 1, member B3 (aldose reductase) | Akr1b3
Database Links Click here for help
Alphafold P15121 (Hs), P45376 (Mm), P07943 (Rn)
BRENDA 1.1.1.21
CATH/Gene3D 3.20.20.100
ChEMBL Target CHEMBL1900 (Hs), CHEMBL3108653 (Mm), CHEMBL2622 (Rn)
Ensembl Gene ENSG00000085662 (Hs), ENSMUSG00000001642 (Mm), ENSRNOG00000009513 (Rn)
Entrez Gene 231 (Hs), 11677 (Mm), 24192 (Rn)
Human Protein Atlas ENSG00000085662 (Hs)
KEGG Enzyme 1.1.1.21
KEGG Gene hsa:231 (Hs), mmu:11677 (Mm), rno:24192 (Rn)
OMIM 103880 (Hs)
Pharos P15121 (Hs)
RefSeq Nucleotide NM_001628 (Hs), NM_009658 (Mm), NM_012498 (Rn)
RefSeq Protein NP_001619 (Hs), NP_033788 (Mm), NP_036630 (Rn)
SynPHARM 82516 (in complex with AK198)
80083 (in complex with lidorestat)
80082 (in complex with sorbinil)
79711 (in complex with tolrestat)
80085 (in complex with zenarestat)
80084 (in complex with zopolrestat)
UniProtKB P15121 (Hs), P45376 (Mm), P07943 (Rn)
Wikipedia AKR1B1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Human aldose reductase (AKLBR1B1) complexed with tolrestat
PDB Id:  2FZD
Ligand:  tolrestat
Resolution:  1.8Å
Species:  Human
References:  4
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human AR complexed with NADP+ and AK198.
PDB Id:  4QXI
Ligand:  AK198
Resolution:  0.87Å
Species:  Human
References:  1
Enzyme Reaction Click here for help
EC Number: 1.1.1.21

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
govorestat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 10.0 pIC50 6
⤷ pIC50 10.0 (IC50 1x10-10 M) [6]
AK198 Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.9 pIC50 1
⤷ pIC50 8.9 (IC50 1.3x10-9 M) [1]
lidorestat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 8.3 pIC50 5
⤷ pIC50 8.3 (IC50 5x10-9 M) [5]
Description: In vitro inhibition of recombinant human aldose reductase expressed in E coli.
tolrestat Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.3 pIC50 3
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [3]
sorbinil Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.3 pIC50 2
⤷ pIC50 5.3 (IC50 5.4x10-6 M) [2]
zenarestat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.0 pIC50 5
⤷ pIC50 5.0 (IC50 9.9x10-6 M) [5]
Description: In vitro inhibition of recombinant human aldehyde reductase
zopolrestat Small molecule or natural product Ligand has a PDB structure Hs Inhibition 4.4 pIC50 5
⤷ pIC50 4.4 (IC50 3.86x10-5 M) [5]
Description: In vitro inhibition of recombinant human aldehyde reductase

References

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1. Fanfrlík J, Ruiz FX, Kadlčíková A, Řezáč J, Cousido-Siah A, Mitschler A, Haldar S, Lepšík M, Kolář MH, Majer P et al.. (2015) The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition. ACS Chem Biol, 10 (7): 1637-42. [PMID:25919404]

2. Oka M, Matsumoto Y, Sugiyama S, Tsuruta N, Matsushima M. (2000) A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography. J Med Chem, 43 (12): 2479-83. [PMID:10882376]

3. Singh SB, Malamas MS, Hohman TC, Nilakantan R, Carper DA, Kitchen D. (2000) Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants. J Med Chem, 43 (6): 1062-70. [PMID:10737739]

4. Steuber H, Zentgraf M, Gerlach C, Sotriffer CA, Heine A, Klebe G. (2006) Expect the unexpected or caveat for drug designers: multiple structure determinations using aldose reductase crystals treated under varying soaking and co-crystallisation conditions. J Mol Biol, 363 (1): 174-87. [PMID:16952371]

5. Van Zandt MC, Jones ML, Gunn DE, Geraci LS, Jones JH, Sawicki DR, Sredy J, Jacot JL, Dicioccio AT, Petrova T et al.. (2005) Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications. J Med Chem, 48 (9): 3141-52. [PMID:15857120]

6. Zhu Y, Lobato AG, Rebelo AP, Canic T, Ortiz-Vega N, Tao X, Syed S, Yanick C, Saporta M, Shy M et al.. (2023) Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency. JCI Insight, 8 (10). [PMID:37014713]

How to cite this page

1.-.-.- Oxidoreductases: aldo-keto reductase family 1 member B. Last modified on 02/04/2024. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2768.