carbonic anhydrase 1 | Carbonic anhydrases | IUPHAR/BPS Guide to PHARMACOLOGY

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carbonic anhydrase 1

Target not currently curated in GtoImmuPdb

Target id: 2597

Nomenclature: carbonic anhydrase 1

Abbreviated Name: CA I

Family: Carbonic anhydrases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 261 8q21.2 CA1 carbonic anhydrase 1
Mouse - 261 3 A1 Car1 carbonic anhydrase 1
Rat - 261 2q23 Car1 carbonic anhydrase 1
Previous and Unofficial Names
Ca1 | Car1 | carbonic anhydrase I
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 4.2.1.1

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
(-)-adrenaline Hs Activation - - 10
KA 90 nM [10]
histamine Hs Activation - - 8
KA of 2100 nM. [8]
L-histidine 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 Hs Inhibition 7.8 pKi 12
pKi 7.8 (Ki 1.5x10-8 M) [12]
methocarbamol Hs Inhibition 7.6 pKi 13
pKi 7.6 (Ki 2.5x10-8 M) [13]
indisulam Hs Inhibition 7.5 pKi 7
pKi 7.5 (Ki 3.1x10-8 M) [7]
methazolamide Hs Inhibition 7.3 – 7.5 pKi 6,12
pKi 7.3 – 7.5 (Ki 5x10-8 – 3.3x10-8 M) [6,12]
zonisamide Hs Inhibition 7.3 pKi 7
pKi 7.3 (Ki 5.6x10-8 M) [7]
acetazolamide Hs Inhibition 6.6 pKi 1,12,14
pKi 6.6 (Ki 2.5x10-7 M) [1,12,14]
topiramate Hs Inhibition 6.6 pKi 12
pKi 6.6 (Ki 2.5x10-7 M) [12]
diclofenamide 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 Hs Inhibition 6.5 pKi
pKi 6.5 (Ki 3.48x10-7 M)
ethoxzolamide 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] Hs Inhibition 6.1 pKi 2
pKi 6.1 (Ki 8.517x10-7 M) [2]
compound 5b [PMID: 31287314] Hs Inhibition 6.1 pKi 2
pKi 6.1 (Ki 9x10-7 M) [2]
sulpiride Hs Inhibition 5.9 pKi 12
pKi 5.9 (Ki 1.2x10-6 M) [12]
gallic acid Hs Inhibition 5.5 pKi 4
pKi 5.5 (Ki 3.2x10-6 M) [4]
SLC-0111 Hs Inhibition 5.3 pKi 3
pKi 5.3 (Ki 5.08x10-6 M) [3]
brinzolamide Hs Inhibition 4.3 pKi 7
pKi 4.3 (Ki 4.5x10-5 M) [7]
dorzolamide 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].

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 23/09/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2597.