carbonic anhydrase 12 | Carbonic anhydrases | IUPHAR/BPS Guide to PHARMACOLOGY

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carbonic anhydrase 12

Target not currently curated in GtoImmuPdb

Target id: 2747

Nomenclature: carbonic anhydrase 12

Abbreviated Name: CA XII

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 - 354 15q22 CA12 carbonic anhydrase 12
Mouse - 354 9 C Car12 carbonic anhydrase 12
Rat - 354 8q24 Ca12 carbonic anhydrase 12
Previous and Unofficial Names
carbonic anhydrase XII | carbonic anyhydrase 12 | Car12
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Human Protein Atlas
KEGG Enzyme
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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
brinzolamide Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3x10-9 M) [6]
methazolamide Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.4x10-9 M) [6]
indisulam Hs Inhibition 8.5 pKi 4
pKi 8.5 (Ki 3.4x10-9 M) [4]
dorzolamide Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.5x10-9 M) [6]
benzolamide Hs Inhibition 8.5 pKi 6
pKi 8.5 (Ki 3.5x10-9 M) [6]
topiramate Hs Inhibition 8.4 pKi 6
pKi 8.4 (Ki 3.8x10-9 M) [6]
sulpiride Hs Inhibition 8.4 pKi 6
pKi 8.4 (Ki 3.9x10-9 M) [6]
chlorthalidone Hs Inhibition 8.4 pKi 5
pKi 8.4 (Ki 4.5x10-9 M) [5]
SLC-0111 Hs Inhibition 8.4 pKi 3
pKi 8.4 (Ki 4.5x10-9 M) [3]
acetazolamide Hs Inhibition 8.2 pKi 1,6
pKi 8.2 (Ki 5.7x10-9 M) [1,6]
valdecoxib Hs Inhibition 7.9 pKi 4
pKi 7.9 (Ki 1.3x10-8 M) [4]
celecoxib Hs Inhibition 7.7 pKi 4
pKi 7.7 (Ki 1.8x10-8 M) [4]
ethoxzolamide Hs Inhibition 7.7 pKi 6
pKi 7.7 (Ki 2.2x10-8 M) [6]
diclofenamide Hs Inhibition 7.3 pKi 6
pKi 7.3 (Ki 5x10-8 M) [6]
compound 5a [PMID: 31287314] Hs Inhibition 6.1 pKi 2
pKi 6.1 (Ki 7.838x10-7 M) [2]
compound 5b [PMID: 31287314] Hs Inhibition <5.0 pKi 2
pKi <5.0 (Ki >1x10-5 M) [2]
zonisamide 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
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 08/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2747.