Target Information
Target General Infomation | |||||
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Target ID |
T53378
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Former ID |
TTDR00209
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Target Name |
Carbonic anhydrase IV
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Gene Name |
CA4
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Synonyms |
CAIV; Carbonate dehydratase IV; Carbonic anhydrase 4; CA4
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Target Type |
Successful
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Disease | Breast cancer [ICD9: 174, 175; ICD10: C50] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Ocular hypertension [ICD9: 365.04; ICD10: H40.0] | |||||
Open-angle glaucoma; Ocular hypertension [ICD9: 365, 365.04; ICD10: H40-H42, H40.0] | |||||
Function |
Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
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BioChemical Class |
Carbon-oxygen lyases
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Target Validation |
T53378
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UniProt ID | |||||
EC Number |
EC 4.2.1.1
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Sequence |
MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTK
AKVDKKLGRFFFSGYDKKQTWTVQNNGHSVMMLLENKASISGGGLPAPYQAKQLHLHWSD LPYKGSEHSLDGEHFAMEMHIVHEKEKGTSRNVKEAQDPEDEIAVLAFLVEAGTQVNEGF QPLVEALSNIPKPEMSTTMAESSLLDLLPKEEKLRHYFRYLGSLTTPTCDEKVVWTVFRE PIQLHREQILAFSQKLYYDKEQTVSMKDNVRPLQQLGQRTVIKSGAPGRPLPWALPALLG PMLACLLAGFLR |
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Structure |
1ZNC; 3F7B; 3F7U; 3FW3
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Drugs and Mode of Action | |||||
Drug(s) | Brinzolamide | Drug Info | Approved | Open-angle glaucoma; Ocular hypertension | [536361], [541878] |
MAFENIDE | Drug Info | Approved | Bacterial infection | [530765] | |
SALICYLATE | Drug Info | Phase 4 | Discovery agent | [524105] | |
Curcumin | Drug Info | Phase 3 | Cancer | [532348], [542031] | |
PARABEN | Drug Info | Phase 3 | Discovery agent | [524059] | |
PHENOL | Drug Info | Phase 2/3 | Discovery agent | [525296] | |
COUMATE | Drug Info | Phase 2 | Breast cancer | [531371] | |
SULFAMIDE | Drug Info | Phase 1 | Discovery agent | [524873] | |
SPERMINE | Drug Info | Terminated | Discovery agent | [542107], [546483] | |
Inhibitor | 1-(3,4-dichlorophenyl)-3-hydroxyurea | Drug Info | [528240] | ||
2,4-Disulfamyltrifluoromethylaniline | Drug Info | [527415] | |||
2-oxo-2H-chromene-3-carboxylic acid | Drug Info | [530514] | |||
2-Propyl-pentanoic acid 4-sulfamoyl-benzyl ester | Drug Info | [526241] | |||
2-Propyl-pentanoic acid 4-sulfamoyl-benzylamide | Drug Info | [526241] | |||
3-Amino-benzenesulfonamide | Drug Info | [527415] | |||
4-(2-Amino-ethyl)-benzenesulfonamide | Drug Info | [527415] | |||
4-Amino-3-bromo-benzenesulfonamide | Drug Info | [527415] | |||
4-Amino-3-chloro-benzenesulfonamide | Drug Info | [527415] | |||
4-Amino-3-fluoro-benzenesulfonamide | Drug Info | [527415] | |||
4-Amino-3-iodo-benzenesulfonamide | Drug Info | [527415] | |||
4-Hydrazino-benzenesulfonamide | Drug Info | [527415] | |||
5-amino-1,3,4-thiadiazole-2-sulfonamide | Drug Info | [531013] | |||
6-(aminomethyl)-2H-chromen-2-one | Drug Info | [530514] | |||
6-(hydroxymethyl)-2H-chromen-2-one | Drug Info | [530514] | |||
6-methyl-2-oxo-2H-chromene-3-carboxylic acid | Drug Info | [530514] | |||
7-(benzyloxy)-2H-chromen-2-one | Drug Info | [530514] | |||
Aminocarbonyl dihydrogen phosphate | Drug Info | [527462] | |||
BENZOLAMIDE | Drug Info | [526877] | |||
Carbamoyl phosphate disodium | Drug Info | [527259] | |||
CATECHIN | Drug Info | [531068] | |||
CATECHOL | Drug Info | [530751] | |||
COUMARIN | Drug Info | [530514] | |||
COUMATE | Drug Info | [529605] | |||
Curcumin | Drug Info | [531068] | |||
Decane-1,10-diyl disulfamate | Drug Info | [530359] | |||
Decyl sulfamate | Drug Info | [530359] | |||
ELLAGIC ACID | Drug Info | [530751] | |||
Ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate | Drug Info | [530514] | |||
FERULIC ACID | Drug Info | [530751] | |||
GALLICACID | Drug Info | [530751] | |||
HERNIARIN | Drug Info | [530514] | |||
Hexane-1,6-diamine | Drug Info | [530998] | |||
MAFENIDE | Drug Info | [527415] | |||
Malonate sodium | Drug Info | [527390] | |||
N-(5-ethyl-1,3,4-thiadiazol-2-yl)sulfamide | Drug Info | [529794] | |||
N-(5-phenyl-1,3,4-thiadiazol-2-yl)sulfamide | Drug Info | [529794] | |||
N-(5-Sulfamoyl-[1,3,4]thiadiazol-2-yl)-benzamide | Drug Info | [526241] | |||
N-(5-tert-butyl-1,3,4-thiadiazol-2-yl)sulfamide | Drug Info | [529794] | |||
N-1,3,4-thiadiazol-2-ylsulfamide | Drug Info | [529794] | |||
N-hydroxysulfonamides | Drug Info | [538135] | |||
N-[5-(ethylthio)-1,3,4-thiadiazol-2-yl]sulfamide | Drug Info | [529794] | |||
N-[5-(methylthio)-1,3,4-thiadiazol-2-yl]sulfamide | Drug Info | [529794] | |||
N1-(naphthalen-1-yl)ethane-1,2-diamine | Drug Info | [530998] | |||
Octane-1,8-diyl disulfamate | Drug Info | [530359] | |||
Octyl sulfamate | Drug Info | [530359] | |||
P-Coumaric Acid | Drug Info | [530751] | |||
PARABEN | Drug Info | [530751] | |||
Pentane-1,5-diamine | Drug Info | [530998] | |||
PHENOL | Drug Info | [531068] | |||
Phenyl Boronic acid | Drug Info | [529905] | |||
Phenyl-phosphonic acid | Drug Info | [527462] | |||
Phenylarsonic acid | Drug Info | [527260] | |||
PYRUVATE SODIUM | Drug Info | [527390] | |||
SALICYLATE | Drug Info | [529562] | |||
SODIUM CITRATE | Drug Info | [527390] | |||
Sodium phenylarsonate | Drug Info | [529905] | |||
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS | Drug Info | [527259] | |||
Sodium sulfamate | Drug Info | [529905] | |||
Sodium trithiocarbonate | Drug Info | [530003] | |||
SPARFOSIC ACID | Drug Info | [527462] | |||
SPERMINE | Drug Info | [530998] | |||
SULFAMATE | Drug Info | [527260] | |||
SULFAMIDE | Drug Info | [530922] | |||
Sulfenamido-sulfonamides | Drug Info | [538055] | |||
Syringic Acid | Drug Info | [530751] | |||
Trisodium phosphate | Drug Info | [527259] | |||
[Cu(CN)2]- | Drug Info | [527492] | |||
[Fe(CN)6]4- | Drug Info | [527492] | |||
Modulator | Brinzolamide | Drug Info | [556264] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Nitrogen metabolism | ||||
Proximal tubule bicarbonate reclamation | |||||
Reactome | Erythrocytes take up carbon dioxide and release oxygen | ||||
Erythrocytes take up oxygen and release carbon dioxide | |||||
Reversible hydration of carbon dioxide | |||||
WikiPathways | Reversible Hydration of Carbon Dioxide | ||||
Uptake of Carbon Dioxide and Release of Oxygen by Erythrocytes | |||||
Uptake of Oxygen and Release of Carbon Dioxide by Erythrocytes | |||||
References | |||||
Ref 524059 | ClinicalTrials.gov (NCT01688479) Trial Comparing Calendula Officinalis With Aqueous Cream "Essex" to Treat Skin Reactions From Radiotherapy of Breast Cancer. U.S. National Institutes of Health. | ||||
Ref 524105 | ClinicalTrials.gov (NCT01712295) 17% Salicylate Versus 17% Salicylate-Ethyl Pyruvate for Plantar Foot Warts. U.S. National Institutes of Health. | ||||
Ref 524873 | ClinicalTrials.gov (NCT02216669) Trial to Determine Optimal Phase II Dose of the Oral Dual CAIX Inhibitor/ Radiosensitizer. U.S. National Institutes of Health. | ||||
Ref 525296 | ClinicalTrials.gov (NCT02527187) Determination of the Sensitivity and Specificity of Prick Test Betula Verrucosa. | ||||
Ref 530765 | J Med Chem. 2010 Apr 8;53(7):2913-26.Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases. | ||||
Ref 531371 | Irosustat: a first-generation steroid sulfatase inhibitor in breast cancer. Expert Rev Anticancer Ther. 2011 Feb;11(2):179-83. | ||||
Ref 532348 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | ||||
Ref 536361 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20. | ||||
Ref 541878 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6797). | ||||
Ref 542031 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7000). | ||||
Ref 526241 | J Med Chem. 2002 Jan 17;45(2):312-20.Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. | ||||
Ref 526877 | Bioorg Med Chem Lett. 2003 Sep 1;13(17):2867-73.Carbonic anhydrase inhibitors: topically acting antiglaucoma sulfonamides incorporating esters and amides of 3- and 4-carboxybenzolamide. | ||||
Ref 527259 | Bioorg Med Chem Lett. 2004 Dec 6;14(23):5763-7.Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with phosphates, carbamoyl phosphate, and the phosphonate antiviral drug foscarnet. | ||||
Ref 527260 | Bioorg Med Chem Lett. 2004 Dec 6;14(23):5769-73.Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions. | ||||
Ref 527390 | Bioorg Med Chem Lett. 2005 Feb 1;15(3):573-8.Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with carboxylates. | ||||
Ref 527415 | Bioorg Med Chem Lett. 2005 Feb 15;15(4):1149-54.Carbonic anhydrase inhibitors. Inhibition of the membrane-bound human and bovine isozymes IV with sulfonamides. | ||||
Ref 527462 | Bioorg Med Chem Lett. 2005 Mar 15;15(6):1683-6.Carbonic anhydrase inhibitors. Interaction of isozymes I, II, IV, V, and IX with organic phosphates and phosphonates. | ||||
Ref 527492 | Bioorg Med Chem Lett. 2005 Apr 1;15(7):1909-13.Carbonic anhydrase inhibitors. Inhibition of isozymes I, II, IV, V and IX with complex fluorides, chlorides and cyanides. | ||||
Ref 528240 | Bioorg Med Chem Lett. 2006 Aug 15;16(16):4316-20. Epub 2006 Jun 12.N-hydroxyurea--a versatile zinc binding function in the design of metalloenzyme inhibitors. | ||||
Ref 529562 | Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. Epub 2008 Jun 13.Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. | ||||
Ref 529605 | Bioorg Med Chem Lett. 2008 Aug 1;18(15):4282-6. Epub 2008 Jul 5.Carbonic anhydrase inhibitors. Interaction of the antitumor sulfamate EMD 486019 with twelve mammalian carbonic anhydrase isoforms: Kinetic and X-ray crystallographic studies. | ||||
Ref 529794 | Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. Epub 2008 Nov 1.Carbonic anhydrase inhibitors: 2-substituted-1,3,4-thiadiazole-5-sulfamides act as powerful and selective inhibitors of the mitochondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrases I, II and IV. | ||||
Ref 529905 | Bioorg Med Chem Lett. 2009 Feb 15;19(4):1155-8. Epub 2008 Dec 25.Carbonic anhydrase inhibitors: the membrane-associated isoform XV is highly inhibited by inorganic anions. | ||||
Ref 530003 | Bioorg Med Chem Lett. 2009 Apr 1;19(7):1855-7. Epub 2009 Feb 26.Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I, II, III, VII and XIII with less investigated inorganic anions. | ||||
Ref 530359 | J Med Chem. 2009 Oct 8;52(19):5990-8.Carbonic anhydrase inhibitors. Comparison of aliphatic sulfamate/bis-sulfamate adducts with isozymes II and IX as a platform for designing tight-binding, more isoform-selective inhibitors. | ||||
Ref 530514 | J Med Chem. 2010 Jan 14;53(1):335-44.Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins. | ||||
Ref 530751 | Bioorg Med Chem. 2010 Mar 15;18(6):2159-64. Epub 2010 Feb 6.Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. | ||||
Ref 530922 | Bioorg Med Chem Lett. 2010 Jun 15;20(12):3601-5. Epub 2010 Apr 28.Carbonic anhydrase inhibitors: crystallographic and solution binding studies for the interaction of a boron-containing aromatic sulfamide with mammalian isoforms I-XV. | ||||
Ref 530998 | J Med Chem. 2010 Aug 12;53(15):5511-22.Polyamines inhibit carbonic anhydrases by anchoring to the zinc-coordinated water molecule. | ||||
Ref 531013 | Bioorg Med Chem Lett. 2010 Aug 1;20(15):4376-81. Epub 2010 Jun 17.Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamideresides in a less utilized binding pocket than most hydrophobic inhibitors. | ||||
Ref 531068 | Bioorg Med Chem Lett. 2010 Sep 1;20(17):5050-3. Epub 2010 Jul 13.Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV. | ||||
Ref 538055 | Sulfenamido-sulfonamides as inhibitors of carbonic anhydrase isozymes I, II and IV. J Enzyme Inhib. 1997 Aug;12(3):175-90. | ||||
Ref 538135 | Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IV with N-hydroxysulfonamides--a novel class of intraocular pressure lowering agents. J Enzyme Inhib. 1998 Jul;13(4):267-84. |
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