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carbonic anhydrase 1

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Target id: 2597

Nomenclature: carbonic anhydrase 1

Abbreviated Name: CA I

Family: Carbonic anhydrases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 261 8q21.2 CA1 carbonic anhydrase 1
Mouse - 261 3 3.18 cM Car1 carbonic anhydrase 1
Rat - 261 2q23 Car1 carbonic anhydrase 1
Previous and Unofficial Names Click here for help
Ca1 | Car1 | carbonic anhydrase I
Database Links Click here for help
Alphafold P00915 (Hs), P13634 (Mm), B0BNN3 (Rn)
BRENDA 4.2.1.1
CATH/Gene3D 3.10.200.10
ChEMBL Target CHEMBL261 (Hs)
DrugBank Target P00915 (Hs)
Ensembl Gene ENSG00000133742 (Hs), ENSMUSG00000027556 (Mm), ENSRNOG00000010698 (Rn)
Entrez Gene 759 (Hs), 12346 (Mm), 310218 (Rn)
Human Protein Atlas ENSG00000133742 (Hs)
KEGG Enzyme 4.2.1.1
KEGG Gene hsa:759 (Hs), mmu:12346 (Mm), rno:310218 (Rn)
OMIM 114800 (Hs)
Pharos P00915 (Hs)
RefSeq Nucleotide NM_001128830 (Hs), NM_009799 (Mm), NM_001107660 (Rn)
RefSeq Protein NP_001122302 (Hs), NP_033929 (Mm), NP_001101130 (Rn)
SynPHARM 78858 (in complex with acetazolamide)
78861 (in complex with methazolamide)
79189 (in complex with topiramate)
UniProtKB P00915 (Hs), P13634 (Mm), B0BNN3 (Rn)
Wikipedia CA1 (Hs)
Enzyme Reaction Click here for help
EC Number: 4.2.1.1

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

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Activation - - 10
⤷ KA 90 nM [10]
histamine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Activation - - 8
⤷ KA of 2100 nM. [8]
L-histidine Small molecule or natural product Click here for species-specific activity table Hs Activation - - 11
⤷ [11]
Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
benzolamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKi 12
⤷ pKi 7.8 (Ki 1.5x10-8 M) [12]
methocarbamol Small molecule or natural product Approved drug Hs Inhibition 7.6 pKi 13
⤷ pKi 7.6 (Ki 2.5x10-8 M) [13]
indisulam Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pKi 7
⤷ pKi 7.5 (Ki 3.1x10-8 M) [7]
methazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.3 – 7.5 pKi 6,12
⤷ pKi 7.3 – 7.5 (Ki 5x10-8 – 3.3x10-8 M) [6,12]
zonisamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pKi 7
⤷ pKi 7.3 (Ki 5.6x10-8 M) [7]
acetazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pKi 1,12,14
⤷ pKi 6.6 (Ki 2.5x10-7 M) [1,12,14]
topiramate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 pKi 12
⤷ pKi 6.6 (Ki 2.5x10-7 M) [12]
diclofenamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.9 – 7.1 pKi 12-13
⤷ pKi 5.9 – 7.1 (Ki 1.2x10-6 – 7.4x10-8 M) [12-13]
chlorthalidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.5 pKi
⤷ pKi 6.5 (Ki 3.48x10-7 M)
ethoxzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.3 – 7.6 pKi 5,12
⤷ pKi 5.3 – 7.6 (Ki 4.9x10-6 – 2.5x10-8 M) [5,12]
compound 5a [PMID: 31287314] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.1 pKi 2
⤷ pKi 6.1 (Ki 8.517x10-7 M) [2]
compound 5b [PMID: 31287314] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pKi 2
⤷ pKi 6.1 (Ki 9x10-7 M) [2]
sulpiride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 5.9 pKi 12
⤷ pKi 5.9 (Ki 1.2x10-6 M) [12]
gallic acid Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.5 pKi 4
⤷ pKi 5.5 (Ki 3.2x10-6 M) [4]
SLC-0111 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.3 pKi 3
⤷ pKi 5.3 (Ki 5.08x10-6 M) [3]
brinzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.3 pKi 7
⤷ pKi 4.3 (Ki 4.5x10-5 M) [7]
dorzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.3 pKi 12
⤷ pKi 4.3 (Ki 5x10-5 M) [12]
Inhibitor Comments
Methazolamide inhibits carbonic anhydrases I, IV and XIV with similar affinity.
Acetazolamide inhibits carbonic anhydrases I, IV and XIV but has 10-fold lower affinity at XIV.
Diclofenamide inhibits carbonic anhydrases I and IV.
Chlorthalidone is an approved drug inhibitor of carbonic anhydrase activity. We have tagged CA VII and XII as the primary targets for this drug as affinity is highest at these two isozymes [9].
Immuno Process Associations
Immuno Process:  Cytokine production & signalling

References

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1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R. (2010) Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg Med Chem Lett, 20 (15): 4376-81. [PMID:20605094]

2. Berrino E, Milazzo L, Micheli L, Vullo D, Angeli A, Bozdag M, Nocentini A, Menicatti M, Bartolucci G, di Cesare Mannelli L et al.. (2019) Synthesis and Evaluation of Carbonic Anhydrase Inhibitors with Carbon Monoxide Releasing Properties for the Management of Rheumatoid Arthritis. J Med Chem, 62 (15): 7233-7249. [PMID:31287314]

3. Congiu C, Onnis V, Deplano A, Balboni G, Dedeoglu N, Supuran CT. (2015) Synthesis of sulfonamides incorporating piperazinyl-ureido moieties and their carbonic anhydrase I, II, IX and XII inhibitory activity. Bioorg Med Chem Lett, 25 (18): 3850-3. [PMID:26233435]

4. Innocenti A, Beyza Oztürk Sarikaya S, Gülçin I, Supuran CT. (2010) Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. Bioorg Med Chem, 18 (6): 2159-64. [PMID:20185318]

5. Innocenti A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT. (2005) Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. Bioorg Med Chem Lett, 15 (4): 1149-54. [PMID:15686931]

6. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT. (2005) Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett, 15 (17): 3828-33. [PMID:16039848]

7. Sethi KK, Vullo D, Verma SM, Tanç M, Carta F, Supuran CT. (2013) Carbonic anhydrase inhibitors: synthesis and inhibition of the human carbonic anhydrase isoforms I, II, VII, IX and XII with benzene sulfonamides incorporating 4,5,6,7-tetrabromophthalimide moiety. Bioorg Med Chem, 21 (19): 5973-82. [PMID:23965175]

8. Tanini D, Capperucci A, Supuran CT, Angeli A. (2019) Sulfur, selenium and tellurium containing amines act as effective carbonic anhydrase activators. Bioorg Chem, 87: 516-522. [PMID:30928874]

9. Temperini C, Cecchi A, Scozzafava A, Supuran CT. (2009) Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem, 17 (3): 1214-21. [PMID:19119014]

10. Temperini C, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT. (2007) Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV. Bioorg Med Chem Lett, 17 (3): 628-35. [PMID:17127057]

11. Temperini C, Scozzafava A, Vullo D, Supuran CT. (2006) Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII, and XIV with l- and d-histidine and crystallographic analysis of their adducts with isoform II: engineering proton-transfer processes within the active site of an enzyme. Chemistry, 12 (27): 7057-66. [PMID:16807956]

12. Vullo D, Innocenti A, Nishimori I, Pastorek J, Scozzafava A, Pastoreková S, Supuran CT. (2005) Carbonic anhydrase inhibitors. Inhibition of the transmembrane isozyme XII with sulfonamides-a new target for the design of antitumor and antiglaucoma drugs?. Bioorg Med Chem Lett, 15 (4): 963-9. [PMID:15686894]

13. Winum JY, Temperini C, El Cheikh K, Innocenti A, Vullo D, Ciattini S, Montero JL, Scozzafava A, Supuran CT. (2006) Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J Med Chem, 49 (24): 7024-31. [PMID:17125255]

14. Zimmerman S, Innocenti A, Casini A, Ferry JG, Scozzafava A, Supuran CT. (2004) Carbonic anhydrase inhibitors. Inhibition of the prokariotic beta and gamma-class enzymes from Archaea with sulfonamides. Bioorg Med Chem Lett, 14 (24): 6001-6. [PMID:15546717]

How to cite this page

Carbonic anhydrases: carbonic anhydrase 1. Last modified on 25/07/2019. Accessed on 10/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2597.