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Record Information
Version2.0
Creation Date2009-07-30 17:59:10 UTC
Update Date2014-12-24 20:26:08 UTC
Accession NumberT3D3536
Identification
Common NameTelithromycin
ClassSmall Molecule
DescriptionTelithromycin, a semi-synthetic erythromycin derivative, belongs to a new chemical class of antibiotics called ketolides. Ketolides have been recently added to the macrolide-lincosamide-streptogramin class of antibiotics. Similar to the macrolide antibiotics, telithromycin prevents bacterial growth by interfering with bacterial protein synthesis. Telithromycin binds to the 50S subunit of the 70S bacterial ribosome and blocks further peptide elongation. Binding occurs simultaneously at to two domains of 23S RNA of the 50S ribosomal subunit, domain II and V, where older macrolides bind only to one. It is used to treat mild to moderate respiratory infections.
Compound Type
  • Amine
  • Anti-Bacterial Agent
  • Drug
  • Ester
  • Ether
  • Ketolide
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
Ketek
Chemical FormulaC43H65N5O10
Average Molecular Mass812.004 g/mol
Monoisotopic Mass811.473 g/mol
CAS Registry Number191114-48-4
IUPAC Name(3aR,4S,7R,9R,10R,11R,13R,15R,15aR)-10-{[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy}-4-ethyl-11-methoxy-3a,7,9,11,13,15-hexamethyl-1-{4-[4-(pyridin-3-yl)-1H-imidazol-1-yl]butyl}-tetradecahydro-1H-oxacyclotetradeca[4,3-d][1,3]oxazole-2,6,8,14-tetrone
Traditional Nametelithromycin
SMILES[H][C@]12N(CCCCN3C=NC(=C3)C3=CN=CC=C3)C(=O)O[C@@]1(C)[C@]([H])(CC)OC(=O)[C@]([H])(C)C(=O)[C@]([H])(C)[C@@]([H])(O[C@]1([H])O[C@]([H])(C)C[C@]([H])(N(C)C)[C@@]1([H])O)[C@@](C)(C[C@@]([H])(C)C(=O)[C@]2([H])C)OC
InChI IdentifierInChI=1S/C43H65N5O10/c1-12-33-43(8)37(48(41(53)58-43)19-14-13-18-47-23-31(45-24-47)30-16-15-17-44-22-30)27(4)34(49)25(2)21-42(7,54-11)38(28(5)35(50)29(6)39(52)56-33)57-40-36(51)32(46(9)10)20-26(3)55-40/h15-17,22-29,32-33,36-38,40,51H,12-14,18-21H2,1-11H3/t25-,26-,27+,28+,29-,32+,33+,36-,37-,38-,40+,42-,43+/m1/s1
InChI KeyInChIKey=LJVAJPDWBABPEJ-RMNISARHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbohydrates and carbohydrate conjugates
Direct ParentAminoglycosides
Alternative Parents
Substituents
  • Aminoglycoside core
  • N-substituted imidazole
  • Oxane
  • Oxazolidinone
  • Pyridine
  • 1,3-dicarbonyl compound
  • Oxazolidine
  • Azole
  • Heteroaromatic compound
  • Carbamic acid ester
  • Imidazole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Lactone
  • Carbonic acid derivative
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Cyclic ketone
  • Ketone
  • 1,2-aminoalcohol
  • Acetal
  • Carboxylic acid derivative
  • Oxacycle
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carbonyl group
  • Organic nitrogen compound
  • Alcohol
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Telithromycin PathwayNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point176-188°C
Boiling PointNot Available
Solubility300 mg/L
LogP3
Predicted Properties
PropertyValueSource
Water Solubility0.028 g/LALOGPS
logP4ALOGPS
logP5.37ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)8.84ChemAxon
pKa (Strongest Basic)7.65ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area171.85 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity214.68 m³·mol⁻¹ChemAxon
Polarizability89.27 ųChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_1) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (TMS_1_5) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0bti-0110009330-a597d6786f2ec155d709JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-2311119000-a3fc63423a63d99a5fb7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udj-5692335100-c9dcfe66d206e059a42aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0ik9-0912217680-c23ce8bf8a7dc6585c65JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0f6x-0913128500-dfbbb5029daf5212939dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ktf-7812694000-d210db4913a3e8fedd3dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0100001190-101d9f97452eadd98caaJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-074i-2400009320-dd1ca952f0b45c335762JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-2900002100-7a252e17a6b4beea42fbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0110001390-4bf88a3178c537fe09a1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-08gi-1900002750-173fb451507d24f93587JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06r2-3910001000-6b208b50ef647efcc9fcJSpectraViewer
Toxicity Profile
Route of ExposureAbsolute bioavailability is approximately 57%. Maximal concentrations are reached 0.5 - 4 hours following oral administration. Food intake does not affected absorption.
Mechanism of ToxicityTelithromycin acts by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g., Streptococcus pneumoniae) in the presence of resistance mediated by methylases (erm genes) that alter the domain V binding site of telithromycin. Telithromycin may also inhibit the assembly of nascent ribosomal units. Compared to erythromycin A, telithromycin binds to the 23S rRNA with 10 times greater affinity in erythromycin-susceptible organisms and 25 times greater affinity in macrolide-resistant strains. This increased binding affinity may be conferred by the C11-12 carbamate side chain of telithromycin. The side chain appears to maintain binding at domain II in the presence of resistance mediated by alterations in domain V.
MetabolismHepatic - estimated 50% metabolized by CYP3A4 and 50% metabolized independent of cytochrome P450 Route of Elimination: The systemically available telithromycin is eliminated by multiple pathways as follows: 7% of the dose is excreted unchanged in feces by biliary and/or intestinal secretion; 13% of the dose is excreted unchanged in urine by renal excretion; and 37% of the dose is metabolized by the liver. Half Life: Main elimination half-life is 2-3 hours; terminal elimination half-life is 10 hours
Toxicity ValuesLD50>2000 mg/kg (PO in rats).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of Pneumococcal infection, acute sinusitis, acute bacterial tonsillitis, acute bronchitis and bronchiolitis, lower respiratory tract infection and lobar (pneumococcal) pneumonia.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsMost common side-effects are gastrointestinal, including diarrhea, nausea, abdominal pain and vomiting. Headache and disturbances in taste also occur. Less common side-effects include palpitations, blurred vision and rashes. [Wikipedia]
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00976
HMDB IDHMDB15111
PubChem Compound ID5462516
ChEMBL IDCHEMBL1136
ChemSpider ID26329513
KEGG IDC12009
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTelithromycin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTelithromycin
References
Synthesis Reference

Suhas Sohani, Mandar Deodhar, Nishant Patel, Manish Patel, Mahesh Davadra, Vinodhamar Kansal, “Process for the Preparation of Telithromycin.” U.S. Patent US20070260066, issued November 08, 2007.

MSDSLink
General References
  1. Clay KD, Hanson JS, Pope SD, Rissmiller RW, Purdum PP 3rd, Banks PM: Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med. 2006 Mar 21;144(6):415-20. Epub 2006 Feb 15. [16481451 ]
  2. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
References
  1. Bearden DT, Neuhauser MM, Garey KW: Telithromycin: an oral ketolide for respiratory infections. Pharmacotherapy. 2001 Oct;21(10):1204-22. [11601667 ]
  2. Zhanel GG, Walters M, Noreddin A, Vercaigne LM, Wierzbowski A, Embil JM, Gin AS, Douthwaite S, Hoban DJ: The ketolides: a critical review. Drugs. 2002;62(12):1771-804. [12149046 ]
  3. Reed M, Wall GC, Shah NP, Heun JM, Hicklin GA: Verapamil toxicity resulting from a probable interaction with telithromycin. Ann Pharmacother. 2005 Feb;39(2):357-60. Epub 2004 Dec 14. [15598962 ]
  4. Shi J, Chapel S, Montay G, Hardy P, Barrett JS, Sica D, Swan SK, Noveck R, Leroy B, Bhargava VO: Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment. Int J Clin Pharmacol Ther. 2005 Mar;43(3):123-33. [15792396 ]
  5. Nguyen M, Chung EP: Telithromycin: the first ketolide antimicrobial. Clin Ther. 2005 Aug;27(8):1144-63. [16199242 ]
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
References
  1. Bearden DT, Neuhauser MM, Garey KW: Telithromycin: an oral ketolide for respiratory infections. Pharmacotherapy. 2001 Oct;21(10):1204-22. [11601667 ]
  2. Zhanel GG, Walters M, Noreddin A, Vercaigne LM, Wierzbowski A, Embil JM, Gin AS, Douthwaite S, Hoban DJ: The ketolides: a critical review. Drugs. 2002;62(12):1771-804. [12149046 ]
  3. Reed M, Wall GC, Shah NP, Heun JM, Hicklin GA: Verapamil toxicity resulting from a probable interaction with telithromycin. Ann Pharmacother. 2005 Feb;39(2):357-60. Epub 2004 Dec 14. [15598962 ]
  4. Shi J, Chapel S, Montay G, Hardy P, Barrett JS, Sica D, Swan SK, Noveck R, Leroy B, Bhargava VO: Effect of ketoconazole on the pharmacokinetics and safety of telithromycin and clarithromycin in older subjects with renal impairment. Int J Clin Pharmacol Ther. 2005 Mar;43(3):123-33. [15792396 ]
  5. Nguyen M, Chung EP: Telithromycin: the first ketolide antimicrobial. Clin Ther. 2005 Aug;27(8):1144-63. [16199242 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Nguyen M, Chung EP: Telithromycin: the first ketolide antimicrobial. Clin Ther. 2005 Aug;27(8):1144-63. [16199242 ]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [19934256 ]
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [19934256 ]
General Function:
Oxygen binding
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010 [Link]
General Function:
Oxygen binding
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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010 [Link]