Cetirizine (T3D2756)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (5)XML
Targets (5)
Record Information
Version2.0
Creation Date2009-07-21 20:26:38 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2756
Identification
Common NameCetirizine
ClassSmall Molecule
DescriptionCetirizine is a medication used for the treatment of allergies, hay fever, angioedema, and hives. It is a second-generation H1-receptor antagonist antihistamine and works by blocking H1 histamine receptors. It is a major metabolite of hydroxyzine, and has the same basic side effects, including dry mouth. A potent second-generation histamine H1 antagonist that is effective in the treatment of allergic rhinitis, chronic urticaria, and pollen-induced asthma. Unlike many traditional antihistamines, it does not cause drowsiness or anticholinergic side effects. Cetirizine hydrochloride is a medication used for the treatment of allergies, hay fever, angioedema, and hives. It is a second-generation H1-receptor antagonist antihistamine and works by blocking H1 histamine receptors. It is a major metabolite of hydroxyzine, and has the same basic side effects, including dry mouth.
Compound Type
  • Amine
  • Anti-Allergic Agent
  • Drug
  • Ether
  • Food Toxin
  • Histamine Antagonist
  • Histamine H1 Antagonist, Non-Sedating
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Alerlisin
Benaday
Cetirizin
Cetirizina
Cetirizine hydrochloride
Cetirizinum
Cetryn
Formistin
Hitrizin
Humex
Reactine
Virlix
Zirtek
Zyrlex
Zyrtec
Chemical FormulaC21H25ClN2O3
Average Molecular Mass388.888 g/mol
Monoisotopic Mass388.155 g/mol
CAS Registry Number83881-51-0
IUPAC Name2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)acetic acid
Traditional Namecetirizine
SMILESOC(=O)COCCN1CCN(CC1)C(C1=CC=CC=C1)C1=CC=C(Cl)C=C1
InChI IdentifierInChI=1/C21H25ClN2O3/c22-19-8-6-18(7-9-19)21(17-4-2-1-3-5-17)24-12-10-23(11-13-24)14-15-27-16-20(25)26/h1-9,21H,10-16H2,(H,25,26)
InChI KeyInChIKey=ZKLPARSLTMPFCP-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Chlorobenzene
  • Halobenzene
  • N-alkylpiperazine
  • Aralkylamine
  • Aryl halide
  • 1,4-diazinane
  • Aryl chloride
  • Piperazine
  • Amino acid
  • Amino acid or derivatives
  • Tertiary amine
  • Tertiary aliphatic amine
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Dialkyl ether
  • Monocarboxylic acid or derivatives
  • Azacycle
  • Ether
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organohalogen compound
  • Amine
  • Organochloride
  • Organonitrogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Skin
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point112.5°C
Boiling PointNot Available
Solubility101 mg/L
LogP2.8
Predicted Properties
PropertyValueSource
Water Solubility0.066 g/LALOGPS
logP2.98ALOGPS
logP0.86ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)3.6ChemAxon
pKa (Strongest Basic)7.79ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area53.01 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity106.87 m³·mol⁻¹ChemAxon
Polarizability41.88 ųChemAxon
Number of Rings3ChemAxon
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, Positivesplash10-0udr-3292000000-e20abaab20740ce81a182017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0uds-7498000000-d6daecf118171395d6b72017-10-06View 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
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-03View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000j-0900000000-9801bb859e79fa9922aa2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-014b559d56b0f32984ff2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-213bd47e17d5ab69ad4b2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-004r-9006000000-f496e22c8e0e293fe98c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-d8a55ab1a7aff0580a912017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-d8a55ab1a7aff0580a912017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-dc957bb6f947575ae4fa2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000b-0900000000-48fc0581ff9fff15e16d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-04ca95fadd952d0aaeb82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-000i-0009000000-014b559d56b0f32984ff2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0009000000-26a7769df28c2325ec532017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , negativesplash10-0006-0009000000-284c2e7b25733d7c98752017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-0009000000-04befed283d691217ba22017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0190000000-14715ff4d57580fbb1662017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0f79-0069000000-431df9c3533b77cf08bc2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0090000000-e042b67e2048318e7dbd2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0udi-0190000000-b0dfb67717c01fd0c0b92017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0gb9-0970000000-e2810b242fefb4a419e72017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-014i-0900000000-72f7cddc4ff6d45f98c02017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0019000000-e2cc239f762011eb0c4d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0w2i-1169000000-185e6899ae017256a7672016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-3391000000-bfd70499959ae71093eb2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0009000000-caf1604c9603d45a67122016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-1119000000-61c40cd9a0e9b76b5e912016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-056r-9162000000-08731719ee47b215e4c72016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral; mean peak plasma concentration (Cmax) of 114 ng/mL at a time (Tmax) of 2.2 hours postdose was observed for cetirizine.
Mechanism of ToxicityCetirizine competes with histamine for binding at H1-receptor sites on the effector cell surface, resulting in suppression of histaminic edema, flare, and pruritus. The low incidence of sedation can be attributed to reduced penetration of cetirizine into the CNS as a result of the less lipophilic carboxyl group on the ethylamine side chain.
Metabolism Half Life: 8.3 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the relief of symptoms associated with seasonal allergic rhinitis, perennial allergic rhinitis and the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria
Minimum Risk LevelNot Available
Health EffectsOverdosage has been reported with ZYRTEC (cetirizine) . In one adult patient who took 150 mg of ZYRTEC (cetirizine) , the patient was somnolent but did not display any other clinical signs or abnormal blood chemistry or hematology results. In an 18 month old pediatric patient who took an overdose of ZYRTEC (cetirizine) (approximately 180 mg), restlessness and irritability were observed initially; this was followed by drowsiness. (13)
SymptomsSomnolence (sleepiness or unusual drowsiness), restlessness, irritability.
TreatmentShould overdose occur, treatment should be symptomatic or supportive, taking into account any concomitantly ingested medications. There is no known specific antidote to Cetirizine. (13)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00341
HMDB IDHMDB05032
PubChem Compound ID2678
ChEMBL IDCHEMBL1000
ChemSpider ID2577
KEGG IDC07778
UniProt IDNot Available
OMIM ID
ChEBI ID3561
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCetirizine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCetirizine
References
Synthesis Reference

Manne Reddy, “Polymorphic forms of dihydrochloride salts of cetirizine and processes for preparation thereof.” U.S. Patent US20040186112, issued September 23, 2004.

MSDSLink
General References
  1. Purohit A, Melac M, Pauli G, Frossard N: Comparative activity of cetirizine and desloratadine on histamine-induced wheal-and-flare responses during 24 hours. Ann Allergy Asthma Immunol. 2004 Jun;92(6):635-40. [15237765 ]
  2. Ramboer I, Bumtbacea R, Lazarescu D, Radu JR: Cetirizine and loratadine: a comparison using the ED50 in skin reactions. J Int Med Res. 2000 Mar-Apr;28(2):69-77. [10898119 ]
  3. Townley RG, Okada C: Use of cetirizine to investigate non-H1 effects of second-generation antihistamines. Ann Allergy. 1992 Feb;68(2):190-6. [1346737 ]
  4. Brik A, Tashkin DP, Gong H Jr, Dauphinee B, Lee E: Effect of cetirizine, a new histamine H1 antagonist, on airway dynamics and responsiveness to inhaled histamine in mild asthma. J Allergy Clin Immunol. 1987 Jul;80(1):51-6. [2885355 ]
  5. Fadel R, Herpin-Richard N, Rihoux JP, Henocq E: Inhibitory effect of cetirizine 2HCl on eosinophil migration in vivo. Clin Allergy. 1987 Jul;17(4):373-9. [2887304 ]
  6. Tashiro M, Sakurada Y, Iwabuchi K, Mochizuki H, Kato M, Aoki M, Funaki Y, Itoh M, Iwata R, Wong DF, Yanai K: Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol. 2004 Aug;44(8):890-900. [15286093 ]
  7. Petersen LJ, Church MK, Rihoux JP, Skov PS: Measurement of interstitial cetirizine concentrations in human skin: correlation of drug levels with inhibition of histamine-induced skin responses. Allergy. 1999 Jun;54(6):607-11. [10435475 ]
  8. Siergiejko Z, Michalska I, Rogalewska A, Chyrek-Borowska S: [Effect of cetirizine, selective H1 antagonist of histamine on skin and bronchial reactivity and cellular histamine release in allergic diseases]. Pneumonol Alergol Pol. 1992;60(11-12):22-7. [1303774 ]
  9. Purohit A, Duvernelle C, Melac M, Pauli G, Frossard N: Twenty-four hours of activity of cetirizine and fexofenadine in the skin. Ann Allergy Asthma Immunol. 2001 Apr;86(4):387-92. [11345280 ]
  10. Atkins PC, Zweiman B, Moskovitz A, von Allmen C, Ciliberti M: Cellular inflammatory responses and mediator release during early developing late-phase allergic cutaneous inflammatory responses: effects of cetirizine. J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):806-11. [9215249 ]
  11. Simons FE, Murray HE, Simons KJ: Quantitation of H1-receptor antagonists in skin and serum. J Allergy Clin Immunol. 1995 Mar;95(3):759-64. [7897161 ]
  12. Drugs.com [Link]
  13. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histamine H1 receptor
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.00316 uMNot AvailableBindingDB 22890
Inhibitory0.00589 uMNot AvailableBindingDB 22890
Inhibitory0.014 uMNot AvailableBindingDB 22890
Inhibitory0.05 uMNot AvailableBindingDB 22890
Inhibitory0.05012 uMNot AvailableBindingDB 22890
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Christophe B, Carlier B, Gillard M, Chatelain P, Peck M, Massingham R: Histamine H1 receptor antagonism by cetirizine in isolated guinea pig tissues: influence of receptor reserve and dissociation kinetics. Eur J Pharmacol. 2003 May 30;470(1-2):87-94. [12787835 ]
  3. Tashiro M, Sakurada Y, Iwabuchi K, Mochizuki H, Kato M, Aoki M, Funaki Y, Itoh M, Iwata R, Wong DF, Yanai K: Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol. 2004 Aug;44(8):890-900. [15286093 ]
  4. Tillement JP, Testa B, Bree F: Compared pharmacological characteristics in humans of racemic cetirizine and levocetirizine, two histamine H1-receptor antagonists. Biochem Pharmacol. 2003 Oct 1;66(7):1123-6. [14505791 ]
  5. Cavero I, Mestre M, Guillon JM, Heuillet E, Roach AG: Preclinical in vitro cardiac electrophysiology: a method of predicting arrhythmogenic potential of antihistamines in humans? Drug Saf. 1999;21 Suppl 1:19-31; discussion 81-7. [10597865 ]
  6. Tamura T, Masaki S, Ohmori K, Karasawa A: Effect of olopatadine and other histamine H1 receptor antagonists on the skin inflammation induced by repeated topical application of oxazolone in mice. Pharmacology. 2005 Dec;75(1):45-52. Epub 2005 Jun 7. [15942272 ]
  7. Gillard M, Van Der Perren C, Moguilevsky N, Massingham R, Chatelain P: Binding characteristics of cetirizine and levocetirizine to human H(1) histamine receptors: contribution of Lys(191) and Thr(194). Mol Pharmacol. 2002 Feb;61(2):391-9. [11809864 ]
  8. Lewis TA, Bayless L, DiPesa AJ, Eckman JB, Gillard M, Libertine L, Scannell RT, Wypij DM, Young MA: 5-Lipoxygenase inhibition by N-hydroxycarbamates in dual-function compounds. Bioorg Med Chem Lett. 2005 Feb 15;15(4):1083-5. [15686917 ]
  9. Lewis TA, Bayless L, Eckman JB, Ellis JL, Grewal G, Libertine L, Marie Nicolas J, Scannell RT, Wels BF, Wenberg K, Wypij DM: 5-lipoxygenase inhibitors with histamine H(1) receptor antagonist activity. Bioorg Med Chem Lett. 2004 May 3;14(9):2265-8. [15081022 ]
  10. Lewis TA, Young MA, Arrington MP, Bayless L, Cai X, Collart P, Eckman JB, Ellis JL, Ene DG, Libertine L, Nicolas JM, Scannell RT, Wels BF, Wenberg K, Wypij DM: Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4. [15482930 ]
  11. Morphy R, Rankovic Z: Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43. [16220969 ]
  12. Janssens F, Leenaerts J, Diels G, De Boeck B, Megens A, Langlois X, van Rossem K, Beetens J, Borgers M: Norpiperidine imidazoazepines as a new class of potent, selective, and nonsedative H1 antihistamines. J Med Chem. 2005 Mar 24;48(6):2154-66. [15771458 ]
  13. Jongejan A, Bruysters M, Ballesteros JA, Haaksma E, Bakker RA, Pardo L, Leurs R: Linking agonist binding to histamine H1 receptor activation. Nat Chem Biol. 2005 Jul;1(2):98-103. Epub 2005 Jun 19. [16408006 ]
Target Details
2. Potassium voltage-gated channel subfamily H member 2
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5030.2 uMNot AvailableBindingDB 22890
IC50108 uMNot AvailableBindingDB 22890
IC50>30 uMNot AvailableBindingDB 22890
References
  1. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
  2. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  3. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  4. Du LP, Tsai KC, Li MY, You QD, Xia L: The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents. Bioorg Med Chem Lett. 2004 Sep 20;14(18):4771-7. [15324906 ]
  5. Zhu BY, Jia ZJ, Zhang P, Su T, Huang W, Goldman E, Tumas D, Kadambi V, Eddy P, Sinha U, Scarborough RM, Song Y: Inhibitory effect of carboxylic acid group on hERG binding. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5507-12. Epub 2006 Aug 22. [16931010 ]
Target Details
3. Angiopoietin-1 receptor
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. Has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. Required for normal angiogenesis and heart development during embryogenesis. Required for post-natal hematopoiesis. After birth, activates or inhibits angiogenesis, depending on the context. Inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In quiescent vessels, ANGPT1 oligomers recruit TEK to cell-cell contacts, forming complexes with TEK molecules from adjoining cells, and this leads to preferential activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascades. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1, and ultimately to the stimulation of sprouting angiogenesis. ANGPT1 signaling triggers receptor dimerization and autophosphorylation at specific tyrosine residues that then serve as binding sites for scaffold proteins and effectors. Signaling is modulated by ANGPT2 that has lower affinity for TEK, can promote TEK autophosphorylation in the absence of ANGPT1, but inhibits ANGPT1-mediated signaling by competing for the same binding site. Signaling is also modulated by formation of heterodimers with TIE1, and by proteolytic processing that gives rise to a soluble TEK extracellular domain. The soluble extracellular domain modulates signaling by functioning as decoy receptor for angiopoietins. TEK phosphorylates DOK2, GRB7, GRB14, PIK3R1; SHC1 and TIE1.
Gene Name:
TEK
Uniprot ID:
Q02763
Molecular Weight:
125829.005 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation90 uMNot AvailableBindingDB 22890
References
  1. Gong XW, Mai JH, Xu YH: Discovery of loperamide as an antagonist of angiopoietin1 and angiopoietin2 by virtual screening. Bioorg Med Chem Lett. 2012 Apr 1;22(7):2388-92. doi: 10.1016/j.bmcl.2012.02.036. Epub 2012 Feb 22. [22406116 ]
Target Details
4. Histamine H4 receptor
General Function:
Histamine receptor activity
Specific Function:
The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist).
Gene Name:
HRH4
Uniprot ID:
Q9H3N8
Molecular Weight:
44495.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 22890
References
  1. Lim HD, van Rijn RM, Ling P, Bakker RA, Thurmond RL, Leurs R: Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21. Epub 2005 Jun 9. [15947036 ]
Target Details
5. Multidrug and toxin extrusion protein 1
General Function:
Monovalent cation:proton antiporter activity
Specific Function:
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
Gene Name:
SLC47A1
Uniprot ID:
Q96FL8
Molecular Weight:
61921.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>500 uMNot AvailableBindingDB 22890
References
  1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]