Cetirizine
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Basic Info
| Common Name | Cetirizine(F04748) |
| 2D Structure | |
| Description | Cetirizine 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. |
| FRCD ID | F04748 |
| CAS Number | 83881-51-0 |
| PubChem CID | 2678 |
| Formula | C21H25ClN2O3 |
| IUPAC Name | 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid |
| InChI Key | ZKLPARSLTMPFCP-UHFFFAOYSA-N |
| InChI | InChI=1S/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) |
| Canonical SMILES | C1CN(CCN1CCOCC(=O)O)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl |
| Isomeric SMILES | C1CN(CCN1CCOCC(=O)O)C(C2=CC=CC=C2)C3=CC=C(C=C3)Cl |
| Wikipedia | Cetirizine |
| Synonyms |
cetirizine
83881-51-0
Cetirizina
Virlix
Cetirizinum
Cetirizin
Cetryn
Setir
Ziptek
Zirtek
|
| Classifies |
Predicted: Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Benzene and substituted derivatives |
| Subclass | Diphenylmethanes |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Diphenylmethanes |
| Alternative Parents | |
| Molecular Framework | Aromatic heteromonocyclic compounds |
| 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 |
| Description | This compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 388.892 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 8 |
| Complexity | 443 |
| Monoisotopic Mass | 388.155 |
| Exact Mass | 388.155 |
| XLogP | 1.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 27 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7576 |
| Human Intestinal Absorption | HIA+ | 0.6863 |
| Caco-2 Permeability | Caco2- | 0.5879 |
| P-glycoprotein Substrate | Substrate | 0.7862 |
| P-glycoprotein Inhibitor | Inhibitor | 0.7364 |
| Non-inhibitor | 0.7624 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.5232 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8648 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8408 |
| CYP450 2D6 Substrate | Non-substrate | 0.9116 |
| CYP450 3A4 Substrate | Non-substrate | 0.7000 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9070 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8885 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.9465 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6917 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8660 |
| Inhibitor | 0.6517 | |
| AMES Toxicity | Non AMES toxic | 0.7815 |
| Carcinogens | Non-carcinogens | 0.9426 |
| Fish Toxicity | High FHMT | 0.7963 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9967 |
| Honey Bee Toxicity | Low HBT | 0.8790 |
| Biodegradation | Not ready biodegradable | 0.9974 |
| Acute Oral Toxicity | III | 0.7374 |
| Carcinogenicity (Three-class) | Non-required | 0.5927 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.3861 | LogS |
| Caco-2 Permeability | 0.6594 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.6841 | LD50, mol/kg |
| Fish Toxicity | 1.8479 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9770 | pIGC50, ug/L |
Targets
- 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
References
- 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 ]
- 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
References
- 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 ]
- 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
References
- 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 ]
- 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
- Mechanism of Action:
- Cetirizine competes with histamine for binding at H<sub>1</sub>-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.
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
- 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
References
- 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 ]