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carbonic anhydrase 12

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Target not currently curated in GtoImmuPdb

Target id: 2747

Nomenclature: carbonic anhydrase 12

Abbreviated Name: CA XII

Family: Carbonic anhydrases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 354 15q22.2 CA12 carbonic anhydrase 12
Mouse 1 354 9 C Car12 carbonic anhydrase 12
Rat - 354 8q24 Ca12 carbonic anhydrase 12
Previous and Unofficial Names Click here for help
carbonic anhydrase XII | carbonic anyhydrase 12 | Car12
Database Links Click here for help
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Human Protein Atlas
KEGG Enzyme
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
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
brinzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3x10-9 M) [6]
methazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.4x10-9 M) [6]
indisulam Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 4
pKi 8.5 (Ki 3.4x10-9 M) [4]
dorzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.5x10-9 M) [6]
benzolamide Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.5x10-9 M) [6]
topiramate Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pKi 6
pKi 8.4 (Ki 3.8x10-9 M) [6]
sulpiride Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.4 pKi 6
pKi 8.4 (Ki 3.9x10-9 M) [6]
chlorthalidone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Inhibition 8.4 pKi 5
pKi 8.4 (Ki 4.5x10-9 M) [5]
SLC-0111 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.5x10-9 M) [3]
acetazolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.2 pKi 1,6
pKi 8.2 (Ki 5.7x10-9 M) [1,6]
valdecoxib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pKi 4
pKi 7.9 (Ki 1.3x10-8 M) [4]
celecoxib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.7 pKi 4
pKi 7.7 (Ki 1.8x10-8 M) [4]
ethoxzolamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 pKi 6
pKi 7.7 (Ki 2.2x10-8 M) [6]
diclofenamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.3 pKi 6
pKi 7.3 (Ki 5x10-8 M) [6]
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 7.838x10-7 M) [2]
compound 5b [PMID: 31287314] Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition <5.0 pKi 2
pKi <5.0 (Ki >1x10-5 M) [2]
zonisamide Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.0 pKi 4
pKi 5.0 (Ki 1.1x10-5 M) [4]
Inhibitor Comments
Carbonic anhydrase (CA) inhibitors are active over a number of CA isozymes. We tag those isozymes with the highest drug affinity as the primary molecular target of each of the drugs, with the caveat that the drugs interact with other CA isozymes.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Hyperchlorhidrosis, isolated
OMIM: 143860
General Comments
CA XII is expressed predominantly in the hypoxic tumour microenvironment, and it is a validated target for anti-tumour chemotherapeutic development.

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. 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]

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. 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]

How to cite this page

Carbonic anhydrases: carbonic anhydrase 12. Last modified on 24/07/2019. Accessed on 30/11/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2747.