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carbonic anhydrase 4

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Target not currently curated in GtoImmuPdb

Target id: 2599

Nomenclature: carbonic anhydrase 4

Abbreviated Name: CA IV

Family: Carbonic anhydrases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 312 17q23.1 CA4 carbonic anhydrase 4
Mouse - 305 11 C Car4 carbonic anhydrase 4
Rat - 309 10q26 Car4 carbonic anhydrase 4
Previous and Unofficial Names Click here for help
Ca4 | CAIV | Car4 | carbonic anhydrase IV
Database Links Click here for help
Alphafold P22748 (Hs), Q64444 (Mm), P48284 (Rn)
BRENDA 4.2.1.1
CATH/Gene3D 3.10.200.10
ChEMBL Target CHEMBL3729 (Hs)
DrugBank Target P22748 (Hs)
Ensembl Gene ENSG00000167434 (Hs), ENSMUSG00000000805 (Mm), ENSRNOG00000002916 (Rn)
Entrez Gene 762 (Hs), 12351 (Mm), 29242 (Rn)
Human Protein Atlas ENSG00000167434 (Hs)
KEGG Enzyme 4.2.1.1
KEGG Gene hsa:762 (Hs), mmu:12351 (Mm), rno:29242 (Rn)
OMIM 114760 (Hs)
Orphanet ORPHA119122 (Hs)
Pharos P22748 (Hs)
RefSeq Nucleotide NM_000717 (Hs), NM_007607 (Mm), NM_019174 (Rn)
RefSeq Protein NP_000708 (Hs), NP_031633 (Mm), NP_062047 (Rn)
UniProtKB P22748 (Hs), Q64444 (Mm), P48284 (Rn)
Wikipedia CA4 (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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
methazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 7.6 pKi 4
⤷ pKi 7.6 (Ki 2.4x10-8 M) [4]
topiramate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKi 4
⤷ pKi 7.4 (Ki 4.3x10-8 M) [4]
acetazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.1 – 7.6 pKi 1,6
⤷ pKi 7.1 – 7.6 (Ki 7.4x10-8 – 2.5x10-8 M) [1,6]
salvianolic acid A Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pKi 3
⤷ pKi 7.2 (Ki 6.69x10-8 M) [3]
chlorthalidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 6.7 pKi 5
⤷ pKi 6.7 (Ki 1.96x10-7 M) [5]
compound 5b [PMID: 31287314] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.0 pKi 2
⤷ pKi 6.0 (Ki 9.291x10-7 M) [2]
compound 5a [PMID: 31287314] Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pKi 2
⤷ pKi <5.0 (Ki >1x10-5 M) [2]
diclofenamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 4.8 pKi 7
⤷ pKi 4.8 (Ki 1.5x10-5 M) [7]
Inhibitor Comments
Acetazolamide inhibits carbonic anhydrases I, IV and XIV, but has 10-fold lower affinity for XIV.Bbr>Methazolamide inhibits carbonic anhydrases I, IV and XIV with similar affinity.
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 [5].
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Retinitis pigmentosa 17; RP17
Synonyms: Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology: DOID:10584
OMIM: 600852
Orphanet: ORPHA791

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. Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT. (2015) New natural product carbonic anhydrase inhibitors incorporating phenol moieties. Bioorg Med Chem, 23 (22): 7219-25. [PMID:26498393]

4. 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]

5. 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]

6. Turkmen H, Durgun M, Yilmaztekin S, Emul M, Innocenti A, Vullo D, Scozzafava A, Supuran CT. (2005) Carbonic anhydrase inhibitors. Novel sulfanilamide/acetazolamide derivatives obtained by the tail approach and their interaction with the cytosolic isozymes I and II, and the tumor-associated isozyme IX. Bioorg Med Chem Lett, 15 (2): 367-72. [PMID:15603956]

7. 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]

How to cite this page

Carbonic anhydrases: carbonic anhydrase 4. Last modified on 16/01/2024. Accessed on 13/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2599.