T3DB: Terfenadine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (11)XML

Targets (11)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:39 UTC

Update Date

2014-12-24 20:25:51 UTC

Accession Number

T3D2757

Identification

Common Name

Terfenadine

Class

Small Molecule

Description

Terfenadine is only found in individuals that have used or taken this drug. In the U.S., Terfenadine was superseded by fexofenadine in the 1990s due to the risk of cardiac arrhythmia caused by QT interval prolongation.Terfenadine competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of terfenadine to H1-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier, CNS depression is minimal.

Compound Type

Amine
Anti-Allergic Agent
Anti-Arrhythmia Agent
Drug
Histamine Antagonist
Histamine H1 Antagonist, Non-Sedating
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(RS)-1-(4-tert-butylphenyl)-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}-butan-1-ol
Bronal
Daylert
Seldane
Servinin
Teldane
Terfed
Terfenadin
Terfenadin AL
Terfenadina
Terfénadine
Terfenadine FLX
Terfenadinum
Terfin
Ternadin
Trexyl
Triludan

Chemical Formula

C₃₂H₄₁NO₂

Average Molecular Mass

471.673 g/mol

Monoisotopic Mass

471.314 g/mol

CAS Registry Number

50679-08-8

IUPAC Name

1-(4-tert-butylphenyl)-4-[4-(hydroxydiphenylmethyl)piperidin-1-yl]butan-1-ol

Traditional Name

terfenadine

SMILES

CC(C)(C)C1=CC=C(C=C1)C(O)CCCN1CCC(CC1)C(O)(C1=CC=CC=C1)C1=CC=CC=C1

InChI Identifier

InChI=1/C32H41NO2/c1-31(2,3)26-18-16-25(17-19-26)30(34)15-10-22-33-23-20-29(21-24-33)32(35,27-11-6-4-7-12-27)28-13-8-5-9-14-28/h4-9,11-14,16-19,29-30,34-35H,10,15,20-24H2,1-3H3

InChI Key

InChIKey=GUGOEEXESWIERI-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.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Diphenylmethanes

Direct Parent

Diphenylmethanes

Alternative Parents

Substituents

Diphenylmethane
Phenylbutylamine
Phenylpropane
Aralkylamine
Piperidine
Tertiary alcohol
Tertiary aliphatic amine
Tertiary amine
Secondary alcohol
Organoheterocyclic compound
Azacycle
Aromatic alcohol
Alcohol
Hydrocarbon derivative
Organopnictogen compound
Organic oxygen compound
Organooxygen compound
Organonitrogen compound
Organic nitrogen compound
Amine
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

diarylmethane (CHEBI:9453 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Blood
Heart
Liver

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	147°C
Boiling Point	Not Available
Solubility	0.0963 mg/L (at 25°C)
LogP	7.1

Predicted Properties

Property	Value	Source
Water Solubility	0.00046 g/L	ALOGPS
logP	5.89	ALOGPS
logP	6.48	ChemAxon
logS	-6	ALOGPS
pKa (Strongest Acidic)	13.2	ChemAxon
pKa (Strongest Basic)	9.02	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	43.7 Å²	ChemAxon
Rotatable Bond Count	9	ChemAxon
Refractivity	146.27 m³·mol⁻¹	ChemAxon
Polarizability	56.45 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-001i-0922300000-f2ebf7861ae9f28463f9	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-0a4i-1091031000-8a395a9531e2fce637a4	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-0573-2592100000-35fee494c6fb22cf9279	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00di-0000900000-577805b6e639de28dd59	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-00di-0000900000-6ee8ace68773688ab606	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0000900000-8d9a4ec2424b97bb3b80	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-6770900000-9830d37d285444cff791	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0a4i-5920000000-909f0029205fa0a7663f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-000i-2541900000-f3da0c526b0e748b9567	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0a4i-5920000000-98434dfc2057ad8cb2c6	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0a4i-5920000000-3114fcb90f8a2c560570	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-00di-0000900000-6ee8ace68773688ab606	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0000900000-577805b6e639de28dd59	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-000i-6770900000-7d494f82f525a8d1b156	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-000i-0000900000-8d9a4ec2424b97bb3b80	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-000i-6770900000-9830d37d285444cff791	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 50V, Positive	splash10-0a4i-5920000000-909f0029205fa0a7663f	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-000i-6770900000-3ea778438aa61069b40a	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0uk9-0000900000-33f5717b3bed30143d5b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0uki-0543900000-e5659b7fe1e1659acac9	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-03dr-2981000000-03f1a2ca48b1a2d8e769	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0100900000-19b3063632e4afc820d3	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00fr-5561900000-bac14174fc7e7f1ab7f4	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-003u-9870000000-8b66dc183082f6b4a57f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0000900000-9161868ea37af548032e	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0uk9-0003900000-aef17866c8a1837ed79b	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00dl-2944700000-c715fedf12c50f301dff	2021-09-22	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-001i-8890000000-2c6ad1195e498f463cbf	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Oral. On the basis of a mass balance study using 14C labeled terfenadine the oral absorption of terfenadine was estimated to be at least 70%

Mechanism of Toxicity

Terfenadine competes with histamine for binding at H1-receptor sites in the GI tract, uterus, large blood vessels, and bronchial muscle. This reversible binding of terfenadine to H1-receptors suppresses the formation of edema, flare, and pruritus resulting from histaminic activity. As the drug does not readily cross the blood-brain barrier, CNS depression is minimal.

Metabolism

Terfenadine is a prodrug, generally completely metabolized to the active form fexofenadine in the liver by the enzyme cytochrome P450 CYP3A4 isoform. Due to its near complete metabolism by the liver immediately after leaving the gut, terfenadine normally is not measurable in the plasma. (Wikipedia) Half Life: 3.5 hours

Toxicity Values

LD50: 5000 mg/kg (Oral, mouse)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For the treatment of allergic rhinitis, hay fever, and allergic skin disorders.

Minimum Risk Level

Not Available

Health Effects

Cardiotoxic at higher doses. In larger plasma concentrations, it may lead to toxic effects on the heart's rhythm (e.g. ventricular tachycardia and torsades de pointes). (Wikipedia)

Symptoms

Mild (e.g., headache, nausea, confusion), but adverse cardiac events including cardiac arrest, ventricular arrhythmias including torsades de pointes and QT prolongation have been reported.

Treatment

in cases of overdosage, cardiac monitoring for at least 24 hours is recommended and for as long as QTc is prolonged, along with standard measures to remove any unabsorbed drug. Treatment of the signs and symptoms of overdosage should be symptomatic and supportive after the acute stage. (2)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

119569

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Terfenadine

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Terfenadine

References

Synthesis Reference

Timothy G. Fawcett, Christian T. Goralski, David W. Ziettlow, “Preparation of polymorphically pure terfenadine.” U.S. Patent US4742175, issued April, 1975.

MSDS

Link

General References

Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.058 uM	Not Available	BindingDB 50017376
Inhibitory	0.32 uM	Not Available	BindingDB 50017376
IC50	0.03 uM	Not Available	BindingDB 50017376
IC50	0.05 uM	Not Available	BindingDB 50017376
IC50	0.056 uM	Not Available	BindingDB 50017376
IC50	0.129 uM	Not Available	BindingDB 50017376
IC50	0.2 uM	Not Available	BindingDB 50017376
IC50	0.204 uM	Not Available	BindingDB 50017376
IC50	0.312 uM	Not Available	BindingDB 50017376
IC50	56 uM	Not Available	BindingDB 50017376

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Imai YN, Ryu S, Oiki S: Docking model of drug binding to the human ether-a-go-go potassium channel guided by tandem dimer mutant patch-clamp data: a synergic approach. J Med Chem. 2009 Mar 26;52(6):1630-8. doi: 10.1021/jm801236n. [19260734 ]
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 ]
Pearlstein RA, Vaz RJ, Kang J, Chen XL, Preobrazhenskaya M, Shchekotikhin AE, Korolev AM, Lysenkova LN, Miroshnikova OV, Hendrix J, Rampe D: Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg Med Chem Lett. 2003 May 19;13(10):1829-35. [12729675 ]
Pearlstein R, Vaz R, Rampe D: Understanding the structure-activity relationship of the human ether-a-go-go-related gene cardiac K+ channel. A model for bad behavior. J Med Chem. 2003 May 22;46(11):2017-22. [12747773 ]
Mihalic JT, Fan P, Chen X, Chen X, Fu Y, Motani A, Liang L, Lindstrom M, Tang L, Chen JL, Jaen J, Dai K, Li L: Discovery of a novel melanin concentrating hormone receptor 1 (MCHR1) antagonist with reduced hERG inhibition. Bioorg Med Chem Lett. 2012 Jun 1;22(11):3781-5. doi: 10.1016/j.bmcl.2012.04.006. Epub 2012 Apr 7. [22542010 ]
Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
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 ]
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 ]
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 ]
Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
Aslanian R, Piwinski JJ, Zhu X, Priestley T, Sorota S, Du XY, Zhang XS, McLeod RL, West RE, Williams SM, Hey JA: Structural determinants for histamine H(1) affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5043-7. doi: 10.1016/j.bmcl.2009.07.047. Epub 2009 Aug 5. [19660947 ]
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 ]
Zhang HC, Derian CK, McComsey DF, White KB, Ye H, Hecker LR, Li J, Addo MF, Croll D, Eckardt AJ, Smith CE, Li Q, Cheung WM, Conway BR, Emanuel S, Demarest KT, Andrade-Gordon P, Damiano BP, Maryanoff BE: Novel indolylindazolylmaleimides as inhibitors of protein kinase C-beta: synthesis, biological activity, and cardiovascular safety. J Med Chem. 2005 Mar 24;48(6):1725-8. [15771419 ]
Friemel A, Zunkler BJ: Interactions at human ether-a-go-go-related gene channels. Toxicol Sci. 2010 Apr;114(2):346-55. doi: 10.1093/toxsci/kfq011. Epub 2010 Jan 13. [20071423 ]

Target Details

2. 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

Type	Value	Assay Type	Assay Source
Inhibitory	0.04 uM	Not Available	BindingDB 50017376
IC50	0.094 uM	Not Available	BindingDB 50017376
IC50	0.295 uM	Not Available	BindingDB 50017376
IC50	0.563 uM	Not Available	BindingDB 50017376
Dissociation	0.03548 uM	Not Available	BindingDB 50017376

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Kishimoto W, Hiroi T, Sakai K, Funae Y, Igarashi T: Metabolism of epinastine, a histamine H1 receptor antagonist, in human liver microsomes in comparison with that of terfenadine. Res Commun Mol Pathol Pharmacol. 1997 Dec;98(3):273-92. [9485522 ]
Salata JJ, Jurkiewicz NK, Wallace AA, Stupienski RF 3rd, Guinosso PJ Jr, Lynch JJ Jr: Cardiac electrophysiological actions of the histamine H1-receptor antagonists astemizole and terfenadine compared with chlorpheniramine and pyrilamine. Circ Res. 1995 Jan;76(1):110-9. [8001268 ]
Wood-Baker R, Smith R, Holgate ST: A double-blind, placebo controlled study of the effect of the specific histamine H1-receptor antagonist, terfenadine, in chronic severe asthma. Br J Clin Pharmacol. 1995 Jun;39(6):671-5. [7654486 ]
Phillips GD, Polosa R, Holgate ST: The effect of histamine-H1 receptor antagonism with terfenadine on concentration-related AMP-induced bronchoconstriction in asthma. Clin Exp Allergy. 1989 Jul;19(4):405-9. [2569356 ]
Rafferty P, Holgate ST: Terfenadine (Seldane) is a potent and selective histamine H1 receptor antagonist in asthmatic airways. Am Rev Respir Dis. 1987 Jan;135(1):181-4. [2879489 ]
Zhang MQ, Wada Y, Sato F, Timmerman H: (Piperidinylalkoxy)chromones: novel antihistamines with additional antagonistic activity against leukotriene D4. J Med Chem. 1995 Jun 23;38(13):2472-7. [7608912 ]
Abou-Gharbia M, Moyer JA, Nielsen ST, Webb M, Patel U: New antihistamines: substituted piperazine and piperidine derivatives as novel H1-antagonists. J Med Chem. 1995 Sep 29;38(20):4026-32. [7562938 ]
Walsh DA, Franzyshen SK, Yanni JM: Synthesis and antiallergy activity of 4-(diarylhydroxymethyl)-1-[3-(aryloxy)propyl]piperidines and structurally related compounds. J Med Chem. 1989 Jan;32(1):105-18. [2562852 ]
Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Aslanian R, Piwinski JJ, Zhu X, Priestley T, Sorota S, Du XY, Zhang XS, McLeod RL, West RE, Williams SM, Hey JA: Structural determinants for histamine H(1) affinity, hERG affinity and QTc prolongation in a series of terfenadine analogs. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5043-7. doi: 10.1016/j.bmcl.2009.07.047. Epub 2009 Aug 5. [19660947 ]

Target Details

3. Multidrug resistance protein 1

General Function:: Xenobiotic-transporting atpase activity
Specific Function:: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:: ABCB1
Uniprot ID:: P08183
Molecular Weight:: 141477.255 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	1.1 uM	Not Available	BindingDB 50017376
IC50	1.4 uM	Not Available	BindingDB 50017376
IC50	1.8 uM	Not Available	BindingDB 50017376
IC50	2.5 uM	Not Available	BindingDB 50017376
IC50	2.7 uM	Not Available	BindingDB 50017376

References

Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [11716514 ]

Target Details

4. Muscarinic acetylcholine receptor M1

General Function:: Phosphatidylinositol phospholipase c activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM1
Uniprot ID:: P11229
Molecular Weight:: 51420.375 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	2.9 uM	Not Available	BindingDB 50017376

References

Yasuda SU, Yasuda RP: Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51. [10212017 ]
Abou-Gharbia M, Moyer JA, Nielsen ST, Webb M, Patel U: New antihistamines: substituted piperazine and piperidine derivatives as novel H1-antagonists. J Med Chem. 1995 Sep 29;38(20):4026-32. [7562938 ]

Target Details

5. Cytochrome P450 2J2

General Function:: Steroid hydroxylase activity
Specific Function:: This enzyme metabolizes arachidonic acid predominantly via a NADPH-dependent olefin epoxidation to all four regioisomeric cis-epoxyeicosatrienoic acids. One of the predominant enzymes responsible for the epoxidation of endogenous cardiac arachidonic acid pools.
Gene Name:: CYP2J2
Uniprot ID:: P51589
Molecular Weight:: 57610.165 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	8.1 uM	Not Available	BindingDB 50017376

References

Lafite P, Dijols S, Buisson D, Macherey AC, Zeldin DC, Dansette PM, Mansuy D: Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2. Bioorg Med Chem Lett. 2006 May 15;16(10):2777-80. Epub 2006 Feb 21. [16495056 ]

Target Details

6. Cytochrome P450 3A4

General Function:: Vitamin d3 25-hydroxylase activity
Specific Function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular Weight:: 57342.67 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	0.32 uM	Not Available	BindingDB 50017376

References

Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]

Target Details

7. Muscarinic acetylcholine receptor M2

General Function:: G-protein coupled acetylcholine receptor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:: CHRM2
Uniprot ID:: P08172
Molecular Weight:: 51714.605 Da

References

Yasuda SU, Yasuda RP: Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51. [10212017 ]

Target Details

8. Muscarinic acetylcholine receptor M3

General Function:: Receptor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM3
Uniprot ID:: P20309
Molecular Weight:: 66127.445 Da

References

Yasuda SU, Yasuda RP: Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51. [10212017 ]

Target Details

9. Muscarinic acetylcholine receptor M4

General Function:: Guanyl-nucleotide exchange factor activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:: CHRM4
Uniprot ID:: P08173
Molecular Weight:: 53048.65 Da

References

Yasuda SU, Yasuda RP: Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51. [10212017 ]

Target Details

10. Muscarinic acetylcholine receptor M5

General Function:: Phosphatidylinositol phospholipase c activity
Specific Function:: The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:: CHRM5
Uniprot ID:: P08912
Molecular Weight:: 60073.205 Da

References

Yasuda SU, Yasuda RP: Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes. Pharmacotherapy. 1999 Apr;19(4):447-51. [10212017 ]

Target Details

11. Substance-P receptor

General Function:: Tachykinin receptor activity
Specific Function:: This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.
Gene Name:: TACR1
Uniprot ID:: P25103
Molecular Weight:: 46250.5 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
IC50	>10 uM	Not Available	BindingDB 50017376

References

Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

Terfenadine (T3D2757)

Structure for T3D2757: Terfenadine

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