Zonisamide (T3D2928)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (31)XML
Targets (31)
Record Information
Version2.0
Creation Date2009-07-21 20:27:56 UTC
Update Date2014-12-24 20:25:53 UTC
Accession NumberT3D2928
Identification
Common NameZonisamide
ClassSmall Molecule
DescriptionZonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may be a carbonic anhydrase inhibitor although this is not one of the primary mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels leading to a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.
Compound Type
  • Amide
  • Anticonvulsant
  • Antioxidant
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,2-Benzisoxazole-3-methanesulfonamide
3-(Sulfamoylmethyl)-1,2-benzisoxazole
Benzo[D]isoxazol-3-yl-methanesulfonamide
Exceglan
Excegram
Excegran
Zonegran
Zonisamida
Zonisamidum
Chemical FormulaC8H8N2O3S
Average Molecular Mass212.226 g/mol
Monoisotopic Mass212.026 g/mol
CAS Registry Number68291-97-4
IUPAC Name1,2-benzoxazol-3-ylmethanesulfonamide
Traditional Namezonisamide
SMILESNS(=O)(=O)CC1=NOC2=CC=CC=C12
InChI IdentifierInChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)
InChI KeyInChIKey=UBQNRHZMVUUOMG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzisoxazoles. These are aromatic compounds containing a benzene ring fused to an isoxazole ring. Isoxazole is five-membered ring with three carbon atoms, and an oxygen atom next to a nitrogen atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzisoxazoles
Sub ClassNot Available
Direct ParentBenzisoxazoles
Alternative Parents
Substituents
  • Benzisoxazole
  • Organic sulfonic acid amide
  • Organosulfonic acid amide
  • Benzenoid
  • Azole
  • Isoxazole
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Sulfonyl
  • Aminosulfonyl compound
  • Heteroaromatic compound
  • Azacycle
  • Oxacycle
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxide
  • Organosulfur compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point161-163°C
Boiling PointNot Available
Solubility0.8 mg/mL
LogP0.5
Predicted Properties
PropertyValueSource
Water Solubility2.09 g/LALOGPS
logP0.67ALOGPS
logP0.11ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)9.84ChemAxon
pKa (Strongest Basic)-1.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area86.19 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity50.3 m³·mol⁻¹ChemAxon
Polarizability19.48 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-1900000000-073e3341083b72e5e4ce2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0gx0-0940000000-22533c93dd06de52f6a82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-0900000000-c05ae650c884adcaba5a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-0900000000-477908537d156d43e3a92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-0900000000-f537644668fbc9b2e02b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-1900000000-6359b9c8e68ec5477b262017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-3900000000-db3cf8881465259c48ca2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-014i-6900000000-cd4c8b86f36ce38b3a492017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0930000000-a0dd3941aea211aeb2012017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0900000000-88938a9c69a2d4daf36a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-2900000000-3440f1648bff05d21a312017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-5900000000-a727755cf1e18764e9d02017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udj-9600000000-aa8a18a9ab17508f689d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udj-9200000000-41d7e769a93444ba37512017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0gx0-0940000000-22533c93dd06de52f6a82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-014i-6900000000-939416688f52f31150062021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-014i-3900000000-cbdf90b73153e2a0fbe82021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0udi-2900000000-3440f1648bff05d21a312021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-014i-0900000000-5a5537d57ee730d369552021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-014i-1900000000-e876f2ad2510dae90ae92021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0190000000-beb3210644ad8c7d48b52016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-03di-1790000000-685d923694e188b3784f2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-6900000000-84377f08dd399ceffa082016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0190000000-072fa6d7f1016dc5122f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01q9-3970000000-14adb301eed37c18b5f72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-e80af2cb8bf5e38fe7702016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral. Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.
Mechanism of ToxicityZonisamide binds to sodium channels and voltage sensitive calcium channels, which suppresses neuronal depolarization and hypersynchronization. Zonisamide also inhibits carbonic anhydrase to a weaker extent, but such an effect is not thought to contribute substantially to the drug's anticonvulsant activity.
MetabolismPrimarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2–sulfamoylacetyl phenol, respectively. Route of Elimination: Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite. Half Life: 63 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as adjunctive treatment of partial seizures in adults with epilepsy.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
TreatmentNo specific antidotes for Zonisamide overdosage are available. Following a suspected recent overdose, emesis should be induced or gastric lavage performed with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation. (12)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00909
HMDB IDHMDB15045
PubChem Compound ID5734
ChEMBL IDCHEMBL750
ChemSpider ID5532
KEGG IDC07504
UniProt IDNot Available
OMIM ID
ChEBI ID10127
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZonisamide
PDB IDZON
ACToR IDNot Available
Wikipedia LinkZonisamide
References
Synthesis Reference

Tamar Nidam, “Novel sulfonation method for zonisamide intermediate in zonisamide synthesis and their novel crystal forms.” U.S. Patent US20030114682, issued June 19, 2003.

MSDSLink
General References
  1. Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson's disease patients. Neurosci Res. 2001 Dec;41(4):397-9. [11755227 ]
  2. Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR: Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003 Apr 9;289(14):1820-5. [12684361 ]
  3. Hasegawa H: Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital. Curr Med Res Opin. 2004 May;20(5):577-80. [15140322 ]
  4. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  5. Ueda Y, Doi T, Tokumaru J, Willmore LJ: Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6. [12941455 ]
  6. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  7. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  8. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  9. Peters DH, Sorkin EM: Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. 1993 May;45(5):760-87. [7686468 ]
  10. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  11. Drugs.com [Link]
  12. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

Target Details
1. Carbonic anhydrase 2
General Function:
Zinc ion binding
Specific Function:
Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Gene Name:
CA2
Uniprot ID:
P00918
Molecular Weight:
29245.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0103 uMNot AvailableBindingDB 10888
Inhibitory0.035 uMNot AvailableBindingDB 10888
Inhibitory0.0352 uMNot AvailableBindingDB 10888
Inhibitory1.07 uMNot AvailableBindingDB 10888
Inhibitory4.3 uMNot AvailableBindingDB 10888
Inhibitory6.8 uMNot AvailableBindingDB 10888
Inhibitory35 uMNot AvailableBindingDB 10888
Dissociation0.0476 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Shank RP, Smith-Swintosky VL, Maryanoff BE: Carbonic anhydrase inhibition. Insight into the characteristics of zonisamide, topiramate, and the sulfamide cognate of topiramate. J Enzyme Inhib Med Chem. 2008 Apr;23(2):271-6. doi: 10.1080/14756360701507001 . [18343915 ]
  4. De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, Scozzafava A, Wurl M, Supuran CT: Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005 May 2;15(9):2315-20. [15837316 ]
  5. Masuda Y, Karasawa T: Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung. 1993 Apr;43(4):416-8. [8494570 ]
  6. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  7. Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P Jr, Blackburn GM, Supuran CT: Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies. Bioorg Med Chem Lett. 2008 Feb 1;18(3):999-1005. Epub 2007 Dec 15. [18162396 ]
  8. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  9. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  10. Vitale RM, Pedone C, Amodeo P, Antel J, Wurl M, Scozzafava A, Supuran CT, De Simone G: Molecular modeling study for the binding of zonisamide and topiramate to the human mitochondrial carbonic anhydrase isoform VA. Bioorg Med Chem. 2007 Jun 15;15(12):4152-8. Epub 2007 Mar 30. [17420132 ]
  11. Nishimori I, Vullo D, Minakuchi T, Morimoto K, Onishi S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2182-8. Epub 2006 Feb 3. [16459077 ]
  12. Nishimori I, Minakuchi T, Morimoto K, Sano S, Onishi S, Takeuchi H, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. J Med Chem. 2006 Mar 23;49(6):2117-26. [16539401 ]
  13. De Simone G, Vitale RM, Di Fiore A, Pedone C, Scozzafava A, Montero JL, Winum JY, Supuran CT: Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J Med Chem. 2006 Sep 7;49(18):5544-51. [16942027 ]
  14. Poulsen SA, Wilkinson BL, Innocenti A, Vullo D, Supuran CT: Inhibition of human mitochondrial carbonic anhydrases VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide derivatives. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4624-7. doi: 10.1016/j.bmcl.2008.07.010. Epub 2008 Jul 10. [18644716 ]
  15. Smaine FZ, Pacchiano F, Rami M, Barragan-Montero V, Vullo D, Scozzafava A, Winum JY, Supuran CT: 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. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1. [18990571 ]
  16. Isik S, Kockar F, Aydin M, Arslan O, Guler OO, Innocenti A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates. Bioorg Med Chem. 2009 Feb 1;17(3):1158-63. doi: 10.1016/j.bmc.2008.12.035. Epub 2008 Dec 24. [19124253 ]
  17. Guzel O, Innocenti A, Scozzafava A, Salman A, Supuran CT: Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3170-3. doi: 10.1016/j.bmcl.2009.04.123. Epub 2009 May 3. [19435663 ]
  18. Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutte S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [19520577 ]
  19. Carta F, Pothen B, Maresca A, Tiwari M, Singh V, Supuran CT: Carbonic anhydrase inhibitors: inhibition of cytosolic carbonic anhydrase isozymes II and VII with simple aromatic sulfonamides and some azo dyes. Chem Biol Drug Des. 2009 Aug;74(2):196-202. doi: 10.1111/j.1747-0285.2009.00842.x. Epub 2009 Jun 22. [19549076 ]
  20. Lopez M, Paul B, Hofmann A, Morizzi J, Wu QK, Charman SA, Innocenti A, Vullo D, Supuran CT, Poulsen SA: S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. J Med Chem. 2009 Oct 22;52(20):6421-32. doi: 10.1021/jm900914e. [19827837 ]
  21. Carta F, Maresca A, Covarrubias AS, Mowbray SL, Jones TA, Supuran CT: Carbonic anhydrase inhibitors. Characterization and inhibition studies of the most active beta-carbonic anhydrase from Mycobacterium tuberculosis, Rv3588c. Bioorg Med Chem Lett. 2009 Dec 1;19(23):6649-54. doi: 10.1016/j.bmcl.2009.10.009. Epub 2009 Oct 7. [19846301 ]
  22. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  23. Kockar F, Maresca A, Aydin M, Isik S, Turkoglu S, Sinan S, Arslan O, Guler OO, Turan Y, Supuran CT: Mutation of Phe91 to Asn in human carbonic anhydrase I unexpectedly enhanced both catalytic activity and affinity for sulfonamide inhibitors. Bioorg Med Chem. 2010 Aug 1;18(15):5498-503. doi: 10.1016/j.bmc.2010.06.056. Epub 2010 Jun 22. [20624682 ]
  24. Bertucci A, Innocenti A, Scozzafava A, Tambutte S, Zoccola D, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata. Bioorg Med Chem Lett. 2011 Jan 15;21(2):710-4. doi: 10.1016/j.bmcl.2010.11.124. Epub 2010 Dec 4. [21208801 ]
  25. Joseph P, Ouahrani-Bettache S, Montero JL, Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Winum JY, Kohler S, Supuran CT: A new beta-carbonic anhydrase from Brucella suis, its cloning, characterization, and inhibition with sulfonamides and sulfamates, leading to impaired pathogen growth. Bioorg Med Chem. 2011 Feb 1;19(3):1172-8. doi: 10.1016/j.bmc.2010.12.048. Epub 2010 Dec 30. [21251841 ]
  26. Maresca A, Supuran CT: (R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1334-7. doi: 10.1016/j.bmcl.2011.01.050. Epub 2011 Jan 18. [21300547 ]
  27. Davis RA, Hofmann A, Osman A, Hall RA, Muhlschlegel FA, Vullo D, Innocenti A, Supuran CT, Poulsen SA: Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases. J Med Chem. 2011 Mar 24;54(6):1682-92. doi: 10.1021/jm1013242. Epub 2011 Feb 18. [21332115 ]
  28. Cincinelli A, Martellini T, Innocenti A, Scozzafava A, Supuran CT: Purification and inhibition studies with anions and sulfonamides of an alpha-carbonic anhydrase from the Antarctic seal Leptonychotes weddellii. Bioorg Med Chem. 2011 Mar 15;19(6):1847-51. doi: 10.1016/j.bmc.2011.02.015. Epub 2011 Feb 13. [21377369 ]
  29. Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran CT: Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV. J Med Chem. 2011 Jun 9;54(11):3977-81. doi: 10.1021/jm200209n. Epub 2011 May 9. [21506569 ]
  30. Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A: Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12. [22041171 ]
  31. Ohradanova A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ, Worheide G, Supuran CT: Cloning, characterization and sulfonamide inhibition studies of an alpha-carbonic anhydrase from the living fossil sponge Astrosclera willeyana. Bioorg Med Chem. 2012 Feb 15;20(4):1403-10. doi: 10.1016/j.bmc.2012.01.007. Epub 2012 Jan 12. [22285172 ]
  32. Hewitson KS, Vullo D, Scozzafava A, Mastrolorenzo A, Supuran CT: Molecular cloning, characterization, and inhibition studies of a beta-carbonic anhydrase from Malassezia globosa, a potential antidandruff target. J Med Chem. 2012 Apr 12;55(7):3513-20. doi: 10.1021/jm300203r. Epub 2012 Mar 28. [22424239 ]
  33. Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezacova P, Chimirri A: Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-9. doi: 10.1021/jm300112w. Epub 2012 Apr 6. [22443141 ]
  34. Pan P, Vermelho AB, Capaci Rodrigues G, Scozzafava A, Tolvanen ME, Parkkila S, Capasso C, Supuran CT: Cloning, characterization, and sulfonamide and thiol inhibition studies of an alpha-carbonic anhydrase from Trypanosoma cruzi, the causative agent of Chagas disease. J Med Chem. 2013 Feb 28;56(4):1761-71. doi: 10.1021/jm4000616. Epub 2013 Feb 19. [23391336 ]
  35. Balaydin HT, Senturk M, Menzek A: Synthesis and carbonic anhydrase inhibitory properties of novel cyclohexanonyl bromophenol derivatives. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1352-7. doi: 10.1016/j.bmcl.2011.12.069. Epub 2011 Dec 21. [22230050 ]
  36. Ekinci D, Cavdar H, Durdagi S, Talaz O, Senturk M, Supuran CT: Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI. Eur J Med Chem. 2012 Mar;49:68-73. doi: 10.1016/j.ejmech.2011.12.022. Epub 2011 Dec 20. [22245047 ]
  37. Masereel B, Rolin S, Abbate F, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem. 2002 Jan 17;45(2):312-20. [11784136 ]
  38. Maryanoff BE, McComsey DF, Lee J, Smith-Swintosky VL, Wang Y, Minor LK, Todd MJ: Carbonic anhydrase-II inhibition. what are the true enzyme-inhibitory properties of the sulfamide cognate of topiramate? J Med Chem. 2008 Apr 24;51(8):2518-21. doi: 10.1021/jm7015649. Epub 2008 Mar 26. [18363349 ]
  39. Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Supuran CT: Inhibition studies of the beta-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium with sulfonamides and sulfamates. Bioorg Med Chem. 2011 Aug 15;19(16):5023-30. doi: 10.1016/j.bmc.2011.06.038. Epub 2011 Jun 24. [21757360 ]
  40. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
Target Details
2. Carbonic anhydrase 1
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name:
CA1
Uniprot ID:
P00915
Molecular Weight:
28870.0 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.056 uMNot AvailableBindingDB 10888
Inhibitory14.8 uMNot AvailableBindingDB 10888
Inhibitory56 uMNot AvailableBindingDB 10888
References
  1. Masuda Y, Karasawa T: Inhibitory effect of zonisamide on human carbonic anhydrase in vitro. Arzneimittelforschung. 1993 Apr;43(4):416-8. [8494570 ]
  2. Hayakawa T, Higuchi Y, Nigami H, Hattori H: Zonisamide reduces hypoxic-ischemic brain damage in neonatal rats irrespective of its anticonvulsive effect. Eur J Pharmacol. 1994 May 12;257(1-2):131-6. [8082694 ]
  3. Owen AJ, Ijaz S, Miyashita H, Wishart T, Howlett W, Shuaib A: Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study. Brain Res. 1997 Oct 3;770(1-2):115-22. [9372210 ]
  4. Kitano Y, Komiyama C, Makino M, Takasuna K, Satoh H, Aoki T, Kinoshita M, Takazawa A, Yamauchi T, Sakurada S: Anticonvulsant and neuroprotective effects of the novel nootropic agent nefiracetam on kainic acid-induced seizures in rats. Brain Res. 2005 Sep 28;1057(1-2):168-76. [16122714 ]
  5. Nagatomo I, Akasaki Y, Uchida M, Kuchiiwa S, Nakagawa S, Takigawa M: Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse. Brain Res. 1998 Apr 13;789(2):213-20. [9573368 ]
  6. Nishimori I, Vullo D, Minakuchi T, Morimoto K, Onishi S, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning and sulfonamide inhibition studies of a carboxyterminal truncated alpha-carbonic anhydrase from Helicobacter pylori. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2182-8. Epub 2006 Feb 3. [16459077 ]
  7. Nishimori I, Minakuchi T, Morimoto K, Sano S, Onishi S, Takeuchi H, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: DNA cloning and inhibition studies of the alpha-carbonic anhydrase from Helicobacter pylori, a new target for developing sulfonamide and sulfamate gastric drugs. J Med Chem. 2006 Mar 23;49(6):2117-26. [16539401 ]
  8. De Simone G, Vitale RM, Di Fiore A, Pedone C, Scozzafava A, Montero JL, Winum JY, Supuran CT: Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J Med Chem. 2006 Sep 7;49(18):5544-51. [16942027 ]
  9. Poulsen SA, Wilkinson BL, Innocenti A, Vullo D, Supuran CT: Inhibition of human mitochondrial carbonic anhydrases VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide derivatives. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4624-7. doi: 10.1016/j.bmcl.2008.07.010. Epub 2008 Jul 10. [18644716 ]
  10. Smaine FZ, Pacchiano F, Rami M, Barragan-Montero V, Vullo D, Scozzafava A, Winum JY, Supuran CT: 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. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1. [18990571 ]
  11. Isik S, Kockar F, Aydin M, Arslan O, Guler OO, Innocenti A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the beta-class enzyme from the yeast Saccharomyces cerevisiae with sulfonamides and sulfamates. Bioorg Med Chem. 2009 Feb 1;17(3):1158-63. doi: 10.1016/j.bmc.2008.12.035. Epub 2008 Dec 24. [19124253 ]
  12. Guzel O, Innocenti A, Scozzafava A, Salman A, Supuran CT: Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3170-3. doi: 10.1016/j.bmcl.2009.04.123. Epub 2009 May 3. [19435663 ]
  13. Bertucci A, Innocenti A, Zoccola D, Scozzafava A, Tambutte S, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies of a coral secretory isoform by sulfonamides. Bioorg Med Chem. 2009 Jul 15;17(14):5054-8. doi: 10.1016/j.bmc.2009.05.063. Epub 2009 May 30. [19520577 ]
  14. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  15. Lopez M, Paul B, Hofmann A, Morizzi J, Wu QK, Charman SA, Innocenti A, Vullo D, Supuran CT, Poulsen SA: S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. J Med Chem. 2009 Oct 22;52(20):6421-32. doi: 10.1021/jm900914e. [19827837 ]
  16. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  17. Kockar F, Maresca A, Aydin M, Isik S, Turkoglu S, Sinan S, Arslan O, Guler OO, Turan Y, Supuran CT: Mutation of Phe91 to Asn in human carbonic anhydrase I unexpectedly enhanced both catalytic activity and affinity for sulfonamide inhibitors. Bioorg Med Chem. 2010 Aug 1;18(15):5498-503. doi: 10.1016/j.bmc.2010.06.056. Epub 2010 Jun 22. [20624682 ]
  18. Bertucci A, Innocenti A, Scozzafava A, Tambutte S, Zoccola D, Supuran CT: Carbonic anhydrase inhibitors. Inhibition studies with anions and sulfonamides of a new cytosolic enzyme from the scleractinian coral Stylophora pistillata. Bioorg Med Chem Lett. 2011 Jan 15;21(2):710-4. doi: 10.1016/j.bmcl.2010.11.124. Epub 2010 Dec 4. [21208801 ]
  19. Joseph P, Ouahrani-Bettache S, Montero JL, Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Winum JY, Kohler S, Supuran CT: A new beta-carbonic anhydrase from Brucella suis, its cloning, characterization, and inhibition with sulfonamides and sulfamates, leading to impaired pathogen growth. Bioorg Med Chem. 2011 Feb 1;19(3):1172-8. doi: 10.1016/j.bmc.2010.12.048. Epub 2010 Dec 30. [21251841 ]
  20. Maresca A, Supuran CT: (R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1334-7. doi: 10.1016/j.bmcl.2011.01.050. Epub 2011 Jan 18. [21300547 ]
  21. Davis RA, Hofmann A, Osman A, Hall RA, Muhlschlegel FA, Vullo D, Innocenti A, Supuran CT, Poulsen SA: Natural product-based phenols as novel probes for mycobacterial and fungal carbonic anhydrases. J Med Chem. 2011 Mar 24;54(6):1682-92. doi: 10.1021/jm1013242. Epub 2011 Feb 18. [21332115 ]
  22. Cincinelli A, Martellini T, Innocenti A, Scozzafava A, Supuran CT: Purification and inhibition studies with anions and sulfonamides of an alpha-carbonic anhydrase from the Antarctic seal Leptonychotes weddellii. Bioorg Med Chem. 2011 Mar 15;19(6):1847-51. doi: 10.1016/j.bmc.2011.02.015. Epub 2011 Feb 13. [21377369 ]
  23. Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran CT: Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV. J Med Chem. 2011 Jun 9;54(11):3977-81. doi: 10.1021/jm200209n. Epub 2011 May 9. [21506569 ]
  24. Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A: Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12. [22041171 ]
  25. Ohradanova A, Vullo D, Pastorekova S, Pastorek J, Jackson DJ, Worheide G, Supuran CT: Cloning, characterization and sulfonamide inhibition studies of an alpha-carbonic anhydrase from the living fossil sponge Astrosclera willeyana. Bioorg Med Chem. 2012 Feb 15;20(4):1403-10. doi: 10.1016/j.bmc.2012.01.007. Epub 2012 Jan 12. [22285172 ]
  26. Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezacova P, Chimirri A: Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-9. doi: 10.1021/jm300112w. Epub 2012 Apr 6. [22443141 ]
  27. Pan P, Vermelho AB, Capaci Rodrigues G, Scozzafava A, Tolvanen ME, Parkkila S, Capasso C, Supuran CT: Cloning, characterization, and sulfonamide and thiol inhibition studies of an alpha-carbonic anhydrase from Trypanosoma cruzi, the causative agent of Chagas disease. J Med Chem. 2013 Feb 28;56(4):1761-71. doi: 10.1021/jm4000616. Epub 2013 Feb 19. [23391336 ]
  28. Balaydin HT, Senturk M, Menzek A: Synthesis and carbonic anhydrase inhibitory properties of novel cyclohexanonyl bromophenol derivatives. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1352-7. doi: 10.1016/j.bmcl.2011.12.069. Epub 2011 Dec 21. [22230050 ]
  29. Ekinci D, Cavdar H, Durdagi S, Talaz O, Senturk M, Supuran CT: Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI. Eur J Med Chem. 2012 Mar;49:68-73. doi: 10.1016/j.ejmech.2011.12.022. Epub 2011 Dec 20. [22245047 ]
  30. Nishimori I, Minakuchi T, Vullo D, Scozzafava A, Supuran CT: Inhibition studies of the beta-carbonic anhydrases from the bacterial pathogen Salmonella enterica serovar Typhimurium with sulfonamides and sulfamates. Bioorg Med Chem. 2011 Aug 15;19(16):5023-30. doi: 10.1016/j.bmc.2011.06.038. Epub 2011 Jun 24. [21757360 ]
  31. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
Target Details
3. Carbonic anhydrase 5A, mitochondrial
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Low activity.
Gene Name:
CA5A
Uniprot ID:
P35218
Molecular Weight:
34750.21 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.02 uMNot AvailableBindingDB 10888
Inhibitory20 uMNot AvailableBindingDB 10888
Dissociation0.0206 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, Scozzafava A, Wurl M, Supuran CT: Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005 May 2;15(9):2315-20. [15837316 ]
  4. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  5. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  6. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  7. Vitale RM, Pedone C, Amodeo P, Antel J, Wurl M, Scozzafava A, Supuran CT, De Simone G: Molecular modeling study for the binding of zonisamide and topiramate to the human mitochondrial carbonic anhydrase isoform VA. Bioorg Med Chem. 2007 Jun 15;15(12):4152-8. Epub 2007 Mar 30. [17420132 ]
  8. Poulsen SA, Wilkinson BL, Innocenti A, Vullo D, Supuran CT: Inhibition of human mitochondrial carbonic anhydrases VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide derivatives. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4624-7. doi: 10.1016/j.bmcl.2008.07.010. Epub 2008 Jul 10. [18644716 ]
  9. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  10. Maresca A, Supuran CT: (R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1334-7. doi: 10.1016/j.bmcl.2011.01.050. Epub 2011 Jan 18. [21300547 ]
  11. Smaine FZ, Pacchiano F, Rami M, Barragan-Montero V, Vullo D, Scozzafava A, Winum JY, Supuran CT: 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. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1. [18990571 ]
Target Details
4. Carbonic anhydrase 9
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Gene Name:
CA9
Uniprot ID:
Q16790
Molecular Weight:
49697.36 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.005 uMNot AvailableBindingDB 10888
Inhibitory0.0051 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. De Simone G, Vitale RM, Di Fiore A, Pedone C, Scozzafava A, Montero JL, Winum JY, Supuran CT: Carbonic anhydrase inhibitors: Hypoxia-activatable sulfonamides incorporating disulfide bonds that target the tumor-associated isoform IX. J Med Chem. 2006 Sep 7;49(18):5544-51. [16942027 ]
  7. Lopez M, Paul B, Hofmann A, Morizzi J, Wu QK, Charman SA, Innocenti A, Vullo D, Supuran CT, Poulsen SA: S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. J Med Chem. 2009 Oct 22;52(20):6421-32. doi: 10.1021/jm900914e. [19827837 ]
  8. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3828-33. [16039848 ]
  9. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  10. Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A: Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12. [22041171 ]
  11. Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezacova P, Chimirri A: Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-9. doi: 10.1021/jm300112w. Epub 2012 Apr 6. [22443141 ]
Target Details
5. Carbonic anhydrase 14
General Function:
Metal ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA14
Uniprot ID:
Q9ULX7
Molecular Weight:
37667.37 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory5.25 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3828-33. [16039848 ]
  7. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  8. Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran CT: Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV. J Med Chem. 2011 Jun 9;54(11):3977-81. doi: 10.1021/jm200209n. Epub 2011 May 9. [21506569 ]
  9. Gitto R, Damiano FM, De Luca L, Ferro S, Vullo D, Supuran CT, Chimirri A: Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors. Bioorg Med Chem. 2011 Dec 1;19(23):7003-7. doi: 10.1016/j.bmc.2011.10.015. Epub 2011 Oct 12. [22041171 ]
  10. Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezacova P, Chimirri A: Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-9. doi: 10.1021/jm300112w. Epub 2012 Apr 6. [22443141 ]
Target Details
6. Carbonic anhydrase 5B, mitochondrial
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA5B
Uniprot ID:
Q9Y2D0
Molecular Weight:
36433.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory6.033 uMNot AvailableBindingDB 10888
Inhibitory6033 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. De Simone G, Di Fiore A, Menchise V, Pedone C, Antel J, Casini A, Scozzafava A, Wurl M, Supuran CT: Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies. Bioorg Med Chem Lett. 2005 May 2;15(9):2315-20. [15837316 ]
  4. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  5. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  6. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  7. Poulsen SA, Wilkinson BL, Innocenti A, Vullo D, Supuran CT: Inhibition of human mitochondrial carbonic anhydrases VA and VB with para-(4-phenyltriazole-1-yl)-benzenesulfonamide derivatives. Bioorg Med Chem Lett. 2008 Aug 15;18(16):4624-7. doi: 10.1016/j.bmcl.2008.07.010. Epub 2008 Jul 10. [18644716 ]
  8. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  9. Maresca A, Supuran CT: (R)-/(S)-10-camphorsulfonyl-substituted aromatic/heterocyclic sulfonamides selectively inhibit mitochondrial over cytosolic carbonic anhydrases. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1334-7. doi: 10.1016/j.bmcl.2011.01.050. Epub 2011 Jan 18. [21300547 ]
  10. Smaine FZ, Pacchiano F, Rami M, Barragan-Montero V, Vullo D, Scozzafava A, Winum JY, Supuran CT: 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. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1. [18990571 ]
Target Details
7. Carbonic anhydrase 7
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA7
Uniprot ID:
P43166
Molecular Weight:
29658.235 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.117 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Guzel O, Innocenti A, Scozzafava A, Salman A, Supuran CT: Carbonic anhydrase inhibitors. Phenacetyl-, pyridylacetyl- and thienylacetyl-substituted aromatic sulfonamides act as potent and selective isoform VII inhibitors. Bioorg Med Chem Lett. 2009 Jun 15;19(12):3170-3. doi: 10.1016/j.bmcl.2009.04.123. Epub 2009 May 3. [19435663 ]
  7. Carta F, Pothen B, Maresca A, Tiwari M, Singh V, Supuran CT: Carbonic anhydrase inhibitors: inhibition of cytosolic carbonic anhydrase isozymes II and VII with simple aromatic sulfonamides and some azo dyes. Chem Biol Drug Des. 2009 Aug;74(2):196-202. doi: 10.1111/j.1747-0285.2009.00842.x. Epub 2009 Jun 22. [19549076 ]
  8. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  9. Hen N, Bialer M, Yagen B, Maresca A, Aggarwal M, Robbins AH, McKenna R, Scozzafava A, Supuran CT: Anticonvulsant 4-aminobenzenesulfonamide derivatives with branched-alkylamide moieties: X-ray crystallography and inhibition studies of human carbonic anhydrase isoforms I, II, VII, and XIV. J Med Chem. 2011 Jun 9;54(11):3977-81. doi: 10.1021/jm200209n. Epub 2011 May 9. [21506569 ]
  10. Gitto R, Damiano FM, Mader P, De Luca L, Ferro S, Supuran CT, Vullo D, Brynda J, Rezacova P, Chimirri A: Synthesis, structure-activity relationship studies, and X-ray crystallographic analysis of arylsulfonamides as potent carbonic anhydrase inhibitors. J Med Chem. 2012 Apr 26;55(8):3891-9. doi: 10.1021/jm300112w. Epub 2012 Apr 6. [22443141 ]
Target Details
8. Voltage-dependent T-type calcium channel subunit alpha-1H
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1H gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1H
Uniprot ID:
O95180
Molecular Weight:
259160.2 Da
References
  1. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  4. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Murata M: Novel therapeutic effects of the anti-convulsant, zonisamide, on Parkinson's disease. Curr Pharm Des. 2004;10(6):687-93. [14965331 ]
  8. Murata M: Zonisamide: a new drug for Parkinson's disease. Drugs Today (Barc). 2010 Apr;46(4):251-8. doi: 10.1358/dot.2010.46.4.1490077. [20502722 ]
  9. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
  10. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
Target Details
9. Voltage-dependent T-type calcium channel subunit alpha-1I
General Function:
Voltage-gated calcium channel activity
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. Isoform alpha-1I gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes. Gates in voltage ranges similar to, but higher than alpha 1G or alpha 1H (By similarity).
Gene Name:
CACNA1I
Uniprot ID:
Q9P0X4
Molecular Weight:
245100.8 Da
References
  1. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  4. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Murata M: Novel therapeutic effects of the anti-convulsant, zonisamide, on Parkinson's disease. Curr Pharm Des. 2004;10(6):687-93. [14965331 ]
  8. Murata M: Zonisamide: a new drug for Parkinson's disease. Drugs Today (Barc). 2010 Apr;46(4):251-8. doi: 10.1358/dot.2010.46.4.1490077. [20502722 ]
  9. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
  10. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
Target Details
10. Carbonic anhydrase 4
General Function:
Zinc ion binding
Specific 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.
Gene Name:
CA4
Uniprot ID:
P22748
Molecular Weight:
35032.075 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory8.59 uMNot AvailableBindingDB 10888
Inhibitory38.45 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Smaine FZ, Pacchiano F, Rami M, Barragan-Montero V, Vullo D, Scozzafava A, Winum JY, Supuran CT: 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. Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1. [18990571 ]
  7. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  8. Balaydin HT, Senturk M, Menzek A: Synthesis and carbonic anhydrase inhibitory properties of novel cyclohexanonyl bromophenol derivatives. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1352-7. doi: 10.1016/j.bmcl.2011.12.069. Epub 2011 Dec 21. [22230050 ]
  9. Ekinci D, Cavdar H, Durdagi S, Talaz O, Senturk M, Supuran CT: Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI. Eur J Med Chem. 2012 Mar;49:68-73. doi: 10.1016/j.ejmech.2011.12.022. Epub 2011 Dec 20. [22245047 ]
Target Details
11. Carbonic anhydrase 6
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
Gene Name:
CA6
Uniprot ID:
P23280
Molecular Weight:
35366.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.089 uMNot AvailableBindingDB 10888
Inhibitory2.42 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Hilvo M, Salzano AM, Innocenti A, Kulomaa MS, Scozzafava A, Scaloni A, Parkkila S, Supuran CT: Cloning, expression, post-translational modifications and inhibition studies on the latest mammalian carbonic anhydrase isoform, CA XV. J Med Chem. 2009 Feb 12;52(3):646-54. doi: 10.1021/jm801267c. [19193158 ]
  7. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
  8. Balaydin HT, Senturk M, Menzek A: Synthesis and carbonic anhydrase inhibitory properties of novel cyclohexanonyl bromophenol derivatives. Bioorg Med Chem Lett. 2012 Feb 1;22(3):1352-7. doi: 10.1016/j.bmcl.2011.12.069. Epub 2011 Dec 21. [22230050 ]
  9. Ekinci D, Cavdar H, Durdagi S, Talaz O, Senturk M, Supuran CT: Structure-activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI. Eur J Med Chem. 2012 Mar;49:68-73. doi: 10.1016/j.ejmech.2011.12.022. Epub 2011 Dec 20. [22245047 ]
Target Details
12. Amine oxidase [flavin-containing] B
General Function:
Primary amine oxidase activity
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.
Gene Name:
MAOB
Uniprot ID:
P27338
Molecular Weight:
58762.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory3.1 uMNot AvailableBindingDB 10888
References
  1. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  2. Murata M: Novel therapeutic effects of the anti-convulsant, zonisamide, on Parkinson's disease. Curr Pharm Des. 2004;10(6):687-93. [14965331 ]
  3. Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson's disease patients. Neurosci Res. 2001 Dec;41(4):397-9. [11755227 ]
  4. Okada M, Kaneko S, Hirano T, Mizuno K, Kondo T, Otani K, Fukushima Y: Effects of zonisamide on dopaminergic system. Epilepsy Res. 1995 Nov;22(3):193-205. [8991786 ]
  5. Murata M: Zonisamide: a new drug for Parkinson's disease. Drugs Today (Barc). 2010 Apr;46(4):251-8. doi: 10.1358/dot.2010.46.4.1490077. [20502722 ]
  6. Okada M: [Effects of carbamazepine and zonisamide on dopaminergic system in rat striatum and hippocampus]. Nihon Shinkei Seishin Yakurigaku Zasshi. 1994 Oct;14(5):337-54. [7856330 ]
  7. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  8. Binda C, Aldeco M, Mattevi A, Edmondson DE: Interactions of monoamine oxidases with the antiepileptic drug zonisamide: specificity of inhibition and structure of the human monoamine oxidase B complex. J Med Chem. 2011 Feb 10;54(3):909-12. doi: 10.1021/jm101359c. Epub 2010 Dec 22. [21175212 ]
Target Details
13. Carbonic anhydrase 12
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA12
Uniprot ID:
O43570
Molecular Weight:
39450.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory11 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg Med Chem Lett. 2005 Sep 1;15(17):3828-33. [16039848 ]
  7. Lopez M, Paul B, Hofmann A, Morizzi J, Wu QK, Charman SA, Innocenti A, Vullo D, Supuran CT, Poulsen SA: S-glycosyl primary sulfonamides--a new structural class for selective inhibition of cancer-associated carbonic anhydrases. J Med Chem. 2009 Oct 22;52(20):6421-32. doi: 10.1021/jm900914e. [19827837 ]
  8. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
Target Details
14. Carbonic anhydrase 3
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA3
Uniprot ID:
P07451
Molecular Weight:
29557.215 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2200 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Temperini C, Cecchi A, Boyle NA, Scozzafava A, Cabeza JE, Wentworth P Jr, Blackburn GM, Supuran CT: Carbonic anhydrase inhibitors. Interaction of 2-N,N-dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide with 12 mammalian isoforms: kinetic and X-ray crystallographic studies. Bioorg Med Chem Lett. 2008 Feb 1;18(3):999-1005. Epub 2007 Dec 15. [18162396 ]
  5. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  6. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  7. Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [17826101 ]
  8. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
Target Details
15. Sodium channel protein type 11 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:
SCN11A
Uniprot ID:
Q9UI33
Molecular Weight:
204919.66 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
16. Sodium channel protein type 2 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
17. Sodium channel protein type 3 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
18. Sodium channel protein type 4 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
19. Sodium channel protein type 5 subunit alpha
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
20. Sodium channel protein type 9 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:
SCN9A
Uniprot ID:
Q15858
Molecular Weight:
226370.175 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
21. Sodium channel subunit beta-1
General Function:
Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:
SCN1B
Uniprot ID:
Q07699
Molecular Weight:
24706.955 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
22. Sodium channel subunit beta-2
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).
Gene Name:
SCN2B
Uniprot ID:
O60939
Molecular Weight:
24325.69 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
23. Sodium channel subunit beta-3
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Gene Name:
SCN3B
Uniprot ID:
Q9NY72
Molecular Weight:
24702.08 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
24. Sodium channel subunit beta-4
General Function:
Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:
Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
Gene Name:
SCN4B
Uniprot ID:
Q8IWT1
Molecular Weight:
24968.755 Da
References
  1. Janszky J: [Role of zonisamid in treating epilepsy, Parkinson disorders and other neurological diseases]. Ideggyogy Sz. 2009 Nov 30;62(11-12):383-9. [20025128 ]
  2. Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. doi: 10.1517/17425255.4.4.493 . [18433351 ]
  3. Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. doi: 10.1517/14656560903468728. [20001433 ]
  4. Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [14704463 ]
  5. Sonsalla PK, Wong LY, Winnik B, Buckley B: The antiepileptic drug zonisamide inhibits MAO-B and attenuates MPTP toxicity in mice: clinical relevance. Exp Neurol. 2010 Feb;221(2):329-34. doi: 10.1016/j.expneurol.2009.11.018. Epub 2009 Dec 4. [19948168 ]
  6. Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [15511691 ]
  7. Zaccara G, Specchio LM: Long-term safety and effectiveness of zonisamide in the treatment of epilepsy: a review of the literature. Neuropsychiatr Dis Treat. 2009;5:249-59. Epub 2009 May 20. [19557119 ]
Target Details
25. Carbonic anhydrase 13
General Function:
Zinc ion binding
Specific Function:
Reversible hydration of carbon dioxide.
Gene Name:
CA13
Uniprot ID:
Q8N1Q1
Molecular Weight:
29442.895 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.43 uMNot AvailableBindingDB 10888
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
  6. Temperini C, Innocenti A, Scozzafava A, Parkkila S, Supuran CT: The coumarin-binding site in carbonic anhydrase accommodates structurally diverse inhibitors: the antiepileptic lacosamide as an example and lead molecule for novel classes of carbonic anhydrase inhibitors. J Med Chem. 2010 Jan 28;53(2):850-4. doi: 10.1021/jm901524f. [20028100 ]
Target Details
26. Carbonic anhydrase-related protein
General Function:
Zinc ion binding
Specific Function:
Does not have a carbonic anhydrase catalytic activity.
Gene Name:
CA8
Uniprot ID:
P35219
Molecular Weight:
32972.915 Da
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
Target Details
27. Carbonic anhydrase-related protein 10
General Function:
Not Available
Specific Function:
Does not have a catalytic activity.
Gene Name:
CA10
Uniprot ID:
Q9NS85
Molecular Weight:
37562.655 Da
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
Target Details
28. Carbonic anhydrase-related protein 11
General Function:
Not Available
Specific Function:
Does not have a catalytic activity.
Gene Name:
CA11
Uniprot ID:
O75493
Molecular Weight:
36237.885 Da
References
  1. De Simone G, Scozzafava A, Supuran CT: Which carbonic anhydrases are targeted by the antiepileptic sulfonamides and sulfamates? Chem Biol Drug Des. 2009 Sep;74(3):317-21. doi: 10.1111/j.1747-0285.2009.00857.x. [19703035 ]
  2. Supuran CT, Di Fiore A, De Simone G: Carbonic anhydrase inhibitors as emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2008 Jun;13(2):383-92. doi: 10.1517/14728214.13.2.383 . [18537527 ]
  3. Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [18782051 ]
  4. Biton V: Clinical pharmacology and mechanism of action of zonisamide. Clin Neuropharmacol. 2007 Jul-Aug;30(4):230-40. [17762320 ]
  5. Zonisamide: new drug. No advantage in refractory partial epilepsy. Prescrire Int. 2007 Jun;16(89):95-7. [17582922 ]
Target Details
29. Amine oxidase [flavin-containing] A
General Function:
Serotonin binding
Specific Function:
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.
Gene Name:
MAOA
Uniprot ID:
P21397
Molecular Weight:
59681.27 Da
References
  1. Okada M, Kaneko S, Hirano T, Mizuno K, Kondo T, Otani K, Fukushima Y: Effects of zonisamide on dopaminergic system. Epilepsy Res. 1995 Nov;22(3):193-205. [8991786 ]
  2. Murata M: Zonisamide: a new drug for Parkinson's disease. Drugs Today (Barc). 2010 Apr;46(4):251-8. doi: 10.1358/dot.2010.46.4.1490077. [20502722 ]
Target Details
30. Voltage-dependent T-type calcium channel subunit alpha-1G
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1G gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by mibefradil. A particularity of this type of channel is an opening at quite negative potentials and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1G
Uniprot ID:
O43497
Molecular Weight:
262468.62 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
Target Details
31. Sodium channel protein type 1 subunit alpha
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Kanazawa O: Refractory grand mal seizures with onset during infancy including severe myoclonic epilepsy in infancy. Brain Dev. 2001 Nov;23(7):749-56. [11701289 ]