Hydrochlorothiazide (T3D4781)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2014-09-11 05:16:19 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4781
Identification
Common NameHydrochlorothiazide
ClassSmall Molecule
DescriptionA thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.
Compound Type
  • Amide
  • Amine
  • Antihypertensive Agent
  • Diuretic
  • Drug
  • Food Toxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Sodium Chloride Symporter Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
3,4-Dihydrochlorothiazide
Acuretic
Aldactazide
Aldoril
Apo-hydro
Apresazide
Aquarills
Aquarius
Bremil
Caplaril
Capozide
Chlorosulthiadil
Chlorothiazide
Chlorsulfonamidodihydrobenzothiadiazine dioxide
Chlorzide
Cidrex
Dichlorosal
Dichlotiazid
Dichlotride
Diclotride
Dihydrochlorothiazid
Dihydrochlorothiazide
Dihydrochlorothiazidum
Dihydrochlorurit
Dihydrochlorurite
Dihydroxychlorothiazidum
Direma
Disalunil
Diuril
Drenol
Dyazide
Esidrex
Esidrix
Esimil
Fluvin
HCTZ
HCZ
Hidril
Hidrochlortiazid
Hidroronol
Hidrotiazida
Hydril
Hydro-Aquil
Hydro-D
Hydro-Diuril
Hydrochloro Thiazide
Hydrochlorothiazid
Hydrochlorothiazide Intensol
Hydrochlorthiazide
Hydrodiuretic
Hydrodiuril
Hydropres
Hydrosaluric
Hydrothide
Hydrozide
Hypothiazid
Hypothiazide
Hyzaar
Idrotiazide
Inderide
Ivaugan
Jen-Diril
Lopressor HCT
Lotensin HCT
Maschitt
Maxzide
Megadiuril
Microzide
Moduretic
Nefrix
Neo-codema
Neoflumen
Newtolide
Oretic
Panurin
Prinzide
Ro-hydrazide
Ser-Ap-Es
Servithiazid
Thiaretic
Thiuretic
Thlaretic
Timolide
Unipres
Urodiazin
Vaseretic
Vetidrex
Ziac
Zide
Chemical FormulaC7H8ClN3O4S2
Average Molecular Mass297.739 g/mol
Monoisotopic Mass296.964 g/mol
CAS Registry Number58-93-5
IUPAC Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Traditional Name6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
SMILESNS(=O)(=O)C1=CC2=C(NCNS2(=O)=O)C=C1Cl
InChI IdentifierInChI=1S/C7H8ClN3O4S2/c8-4-1-5-7(2-6(4)16(9,12)13)17(14,15)11-3-10-5/h1-2,10-11H,3H2,(H2,9,12,13)
InChI KeyInChIKey=JZUFKLXOESDKRF-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as 1,2,4-benzothiadiazine-1,1-dioxides. These are aromatic heterocyclic compounds containing a 1,2,4-benzothiadiazine ring system with two S=O bonds at the 1-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassThiadiazines
Sub ClassBenzothiadiazines
Direct Parent1,2,4-benzothiadiazine-1,1-dioxides
Alternative Parents
Substituents
  • 1,2,4-benzothiadiazine-1,1-dioxide
  • Secondary aliphatic/aromatic amine
  • Aryl chloride
  • Aryl halide
  • Organosulfonic acid amide
  • Benzenoid
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Secondary amine
  • Azacycle
  • Organic oxide
  • Amine
  • Organopnictogen compound
  • Organosulfur compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Kidney
  • Platelet
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point266-268°C
Boiling PointNot Available
Solubility722 mg/L (at 25°C)
LogP-0.07
Predicted Properties
PropertyValueSource
Water Solubility2.24 g/LALOGPS
logP-0.16ALOGPS
logP-0.58ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)9.09ChemAxon
pKa (Strongest Basic)-2.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area118.36 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity63.11 m³·mol⁻¹ChemAxon
Polarizability25.35 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, Positivesplash10-014i-1490000000-623736f34c52e89bbc882017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View 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-ITFT , negativesplash10-014i-0090000000-7906a6e4cfb51dce13962017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-c44dbed5084dc5df03d82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-976dcb246a2272b225652017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0uxr-1090000000-16e563e592e4a566424d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0fb9-9580000000-3c9227e3df8ed6dc9ae92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9720000000-12525bfcb83ea16119702017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9200000000-df37b796b59f084b02292017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-220666bc28231ad387e82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0002-0090000000-f434c5d8ee94540ec0d22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0uxr-1090000000-8a3c270e0fb285b26f152017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0fb9-9480000000-5f6c5ed1d291d71a0aae2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9520000000-679def33e8239c1382f32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004i-9400000000-c9b80274d62fda64c5312017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-014i-0090000000-0a962453b9e31eec38222017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0002-0090000000-ac2b5d07eaacba87a1812017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0gb9-1090000000-8649018477d708cb6bd72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-004i-9400000000-266cd4efe3deeebe29f32017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-014i-0090000000-bc85dd2515151e4fec032017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-004i-9200000000-0f74393a0813e692bd202021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-004i-9300000000-28e5742a9d4eca7b8b562021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-004i-9320000000-b939e4fba37f7da92d722021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-0fb9-5190000000-04ff81457234f6f9b8e12021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-004i-9200000000-df37b796b59f084b02292021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-004i-9720000000-12525bfcb83ea16119702021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0002-0090000000-220666bc28231ad387e82021-09-20View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00r2-6490000000-3f5d9320308b823c64892014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, DMSO-d6, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 100.40 MHz, DMSO-d6, experimental)Not Available2014-09-23View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of Exposure50-60%
Mechanism of ToxicityHydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.
MetabolismHydrochlorothiazide is not metabolized. Route of Elimination: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. Half Life: 5.6 and 14.8 hours
Toxicity ValuesThe oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (16)
Uses/SourcesFor the treatment of high blood pressure and management of edema.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsThe most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00999
HMDB IDHMDB01928
PubChem Compound ID3639
ChEMBL IDCHEMBL435
ChemSpider ID3513
KEGG IDC07041
UniProt IDNot Available
OMIM ID
ChEBI ID102045
BioCyc ID12-DEHYDRORETICULINIUM
CTD IDNot Available
Stitch IDNot Available
PDB IDHCZ
ACToR IDNot Available
Wikipedia LinkHydrochlorothiazide
References
Synthesis Reference

Frederic J. Nugent, John K. C. Yen, “Process for preparing the combination products of triamterene and hydrochlorothiazide.” U.S. Patent US4804540, issued July, 1987.

MSDSLink
General References
  1. Dimitriadis G, Tegos C, Golfinopoulou L, Roboti C, Raptis S: Furosemide-induced hyperglycaemia: the implication of glycolytic kinases. Horm Metab Res. 1993 Nov;25(11):557-9. [8288156 ]
  2. Vandenheuvel WJ, Gruber VF, Walker RW, Wolf FJ: GLC analysis of hydrochlorothiazide in blood and plasma. J Pharm Sci. 1975 Aug;64(8):1309-12. [1151702 ]
  3. Yamazaki M, Ito Y, Suzuka T, Yaginuma H, Itoh S, Kamada A, Orita Y, Nakahama H, Nakanishi T, Ando A: Biopharmaceutical studies of thiazide diuretics. II. High-performance liquid chromatographic method for determination of hydrochlorothiazide in plasma, urine, blood cells and bile. Chem Pharm Bull (Tokyo). 1984 Jun;32(6):2387-94. [6488407 ]
  4. Germano G, Sanguigni V, Pignatelli P, Caccese D, Lenti L, Ragazzo M, Lauro R, Violi F: Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors. J Hypertens. 2004 Jun;22(6):1151-6. [15167450 ]
  5. Bernik MM, Heimann JC, Nakandakare ER, Cazita PM, Nunes VS, Rocha JC, Neves MQ, Quintao EC: Effects of hydrochlorothiazide and propranolol treatment on chylomicron metabolism in hypertensive objects. Can J Physiol Pharmacol. 2005 Jul;83(7):617-23. [16091787 ]
  6. Splendiani G, Condo S: [Diuretic therapy in heart failure]. G Ital Nefrol. 2006 Jan-Feb;23 Suppl 34:S74-6. [16634001 ]
  7. Dornhorst A, Powell SH, Pensky J: Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion. Lancet. 1985 Jan 19;1(8421):123-6. [2857210 ]
  8. Serradeil-Le Gal C, Lacour C, Valette G, Garcia G, Foulon L, Galindo G, Bankir L, Pouzet B, Guillon G, Barberis C, Chicot D, Jard S, Vilain P, Garcia C, Marty E, Raufaste D, Brossard G, Nisato D, Maffrand JP, Le Fur G: Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. J Clin Invest. 1996 Dec 15;98(12):2729-38. [8981918 ]
  9. Kuo BS, Mandagere A, Osborne DR, Hwang KK: Column-switching high-performance liquid chromatographic (HPLC) determination of hydrochlorothiazide in rat, dog, and human plasma. Pharm Res. 1990 Dec;7(12):1257-61. [2095563 ]
  10. Cubeddu LX, Hoffmann IS, Davila S, Escontrelas C, Morales C, Rios A: Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension. Life Sci. 1986 Dec 22;39(25):2463-74. [3540504 ]
  11. Angelin B: Effect of thiazide treatment on biliary lipid composition in healthy volunteers. Eur J Clin Pharmacol. 1989;37(1):95-6. [2591472 ]
  12. Buttar HS: An overview of the influence of ACE inhibitors on fetal-placental circulation and perinatal development. Mol Cell Biochem. 1997 Nov;176(1-2):61-71. [9406146 ]
  13. Tisdall PA, Moyer TP, Anhalt JP: Liquid-chromatographic detection of thiazide diuretics in urine. Clin Chem. 1980 May;26(6):702-6. [7371146 ]
  14. Beermann B, Fahraeus L, Groschinsky-Grind M, Lindstrom B: Placental transfer of hydrochlorothiazide. Gynecol Obstet Invest. 1980;11(1):45-8. [7390276 ]
  15. Vonaparti A, Kazanis M, Panderi I: Development and validation of a liquid chromatographic/electrospray ionization mass spectrometric method for the determination of benazepril, benazeprilat and hydrochlorothiazide in human plasma. J Mass Spectrom. 2006 May;41(5):593-605. [16541390 ]
  16. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Solute carrier family 12 member 3
General Function:
Transporter activity
Specific Function:
Key mediator of sodium and chloride reabsorption in this nephron segment, accounting for a significant fraction of renal sodium reabsorption.
Gene Name:
SLC12A3
Uniprot ID:
P55017
Molecular Weight:
113138.04 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Ran XW, Wang C, Dai F, Jiang JJ, Tong NW, Li XJ, Liang JZ: [A case of Gitelman's syndrome presenting with severe hypocalcaemia and hypokalemic periodic paralysis]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005 Jul;36(4):583-7. [16078592 ]
  3. Turner ST, Schwartz GL, Chapman AB, Boerwinkle E: WNK1 kinase polymorphism and blood pressure response to a thiazide diuretic. Hypertension. 2005 Oct;46(4):758-65. Epub 2005 Sep 19. [16172412 ]
  4. Abuladze N, Yanagawa N, Lee I, Jo OD, Newman D, Hwang J, Uyemura K, Pushkin A, Modlin RL, Kurtz I: Peripheral blood mononuclear cells express mutated NCCT mRNA in Gitelman's syndrome: evidence for abnormal thiazide-sensitive NaCl cotransport. J Am Soc Nephrol. 1998 May;9(5):819-26. [9596079 ]
  5. Barry EL, Gesek FA, Kaplan MR, Hebert SC, Friedman PA: Expression of the sodium-chloride cotransporter in osteoblast-like cells: effect of thiazide diuretics. Am J Physiol. 1997 Jan;272(1 Pt 1):C109-16. [9038817 ]
  6. Kurschat C, Heering P, Grabensee B: [Gitelman's syndrome: an important differential diagnosis of hypokalemia]. Dtsch Med Wochenschr. 2003 May 30;128(22):1225-8. [12772080 ]
  7. Monroy A, Plata C, Hebert SC, Gamba G: Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000 Jul;279(1):F161-9. [10894798 ]
Target Details
2. 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
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 ]
  3. Meyerson LR, Nesta D: [3H]acetazolamide binding to carbonic anhydrase in normal and transformed cells. Biochem Pharmacol. 1991 Mar 15-Apr 1;41(6-7):995-1000. [1901209 ]
  4. Schaeffer P, Vigne P, Frelin C, Lazdunski M: Identification and pharmacological properties of binding sites for the atypical thiazide diuretic, indapamide. Eur J Pharmacol. 1990 Jul 17;182(3):503-8. [2226620 ]
  5. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
Target Details
3. 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
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [10713865 ]
  2. Couloigner V, Loiseau A, Sterkers O, Amiel C, Ferrary E: Effect of locally applied drugs on the endolymphatic sac potential. Laryngoscope. 1998 Apr;108(4 Pt 1):592-8. [9546276 ]
  3. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
Target Details
4. 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
References
  1. Puscas I, Coltau M, Baican M, Domuta G, Hecht A: Vasodilatory effect of diuretics is dependent on inhibition of vascular smooth muscle carbonic anhydrase by a direct mechanism of action. Drugs Exp Clin Res. 1999;25(6):271-9. [10713865 ]
  2. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
Target Details
5. Calcium-activated potassium channel subunit alpha-1
General Function:
Voltage-gated potassium channel activity
Specific Function:
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
Gene Name:
KCNMA1
Uniprot ID:
Q12791
Molecular Weight:
137558.115 Da
References
  1. Tricarico D, Barbieri M, Mele A, Carbonara G, Camerino DC: Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. FASEB J. 2004 Apr;18(6):760-1. Epub 2004 Feb 6. [14766795 ]
Target Details
6. 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
References
  1. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
Target Details
7. 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
References
  1. Temperini C, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg Med Chem. 2009 Feb 1;17(3):1214-21. doi: 10.1016/j.bmc.2008.12.023. Epub 2008 Dec 24. [19119014 ]
Target Details
8. Retinoic acid receptor gamma
General Function:
Zinc ion binding
Specific Function:
Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, acts mainly as an activator of gene expression due to weak binding to corepressors. Required for limb bud development. In concert with RARA or RARB, required for skeletal growth, matrix homeostasis and growth plate function (By similarity).
Gene Name:
RARG
Uniprot ID:
P13631
Molecular Weight:
50341.405 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.26 uMATG_DR5_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
9. Peroxisome proliferator-activated receptor alpha
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2.
Gene Name:
PPARA
Uniprot ID:
Q07869
Molecular Weight:
52224.595 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.87 uMATG_PPRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]