Tmic
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Record Information
Version2.0
Creation Date2009-07-30 17:59:13 UTC
Update Date2014-12-24 20:26:08 UTC
Accession NumberT3D3543
Identification
Common NameVancomycin
ClassSmall Molecule
DescriptionVancomycin is only found in individuals that have used or taken this drug. It is an antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [PubChem]The bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
Compound Type
  • Amine
  • Anti-Bacterial Agent
  • Drug
  • Ether
  • Glycopeptide Antibacterial
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
COVANC
Vancocin
Vancoled
Vancomicina
Vancomycin HCL
Vancomycine
Vancomycinum
Chemical FormulaC66H75Cl2N9O24
Average Molecular Mass1449.254 g/mol
Monoisotopic Mass1447.430 g/mol
CAS Registry Number1404-90-6
IUPAC Name(1S,2R,18R,19R,22S,25R,28R,40S)-48-{[(2S,3R,4S,5S,6R)-3-{[(2S,4S,5S,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy}-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-22-(carbamoylmethyl)-5,47-dichloro-2,18,32,35,37-pentahydroxy-19-[(2R)-4-methyl-2-(methylamino)pentanamido]-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentaazaoctacyclo[26.14.2.2³,⁶.2¹⁴,¹⁷.1⁸,¹².1²⁹,³³.0¹⁰,²⁵.0³⁴,³⁹]pentaconta-3,5,8,10,12(48),14,16,29(45),30,32,34,36,38,46,49-pentadecaene-40-carboxylic acid
Traditional Namevancomycin
SMILES[H][C@](CC(C)C)(NC)C(O)=N[C@@]1([H])C(O)=N[C@@]([H])(CC(O)=N)C(O)=N[C@]2([H])C3=CC(OC4=C(Cl)C=C(C=C4)[C@@]1([H])O)=C(O[C@]1([H])O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]1([H])O[C@@]1([H])C[C@](C)(N)[C@]([H])(O)[C@]([H])(C)O1)C(OC1=C(Cl)C=C(C=C1)[C@@]([H])(O)[C@]1([H])N=C(O)[C@]([H])(N=C2O)C2=CC(=C(O)C=C2)C2=C(C=C(O)C=C2O)[C@]([H])(N=C1O)C(O)=O)=C3
InChI IdentifierInChI=1S/C66H75Cl2N9O24/c1-23(2)12-34(71-5)58(88)76-49-51(83)26-7-10-38(32(67)14-26)97-40-16-28-17-41(55(40)101-65-56(54(86)53(85)42(22-78)99-65)100-44-21-66(4,70)57(87)24(3)96-44)98-39-11-8-27(15-33(39)68)52(84)50-63(93)75-48(64(94)95)31-18-29(79)19-37(81)45(31)30-13-25(6-9-36(30)80)46(60(90)77-50)74-61(91)47(28)73-59(89)35(20-43(69)82)72-62(49)92/h6-11,13-19,23-24,34-35,42,44,46-54,56-57,65,71,78-81,83-87H,12,20-22,70H2,1-5H3,(H2,69,82)(H,72,92)(H,73,89)(H,74,91)(H,75,93)(H,76,88)(H,77,90)(H,94,95)/t24-,34+,35-,42+,44-,46+,47+,48-,49+,50-,51+,52+,53+,54-,56+,57+,65-,66-/m0/s1
InChI KeyInChIKey=MYPYJXKWCTUITO-LYRMYLQWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cyclic peptides. Cyclic peptides are compounds containing a cyclic moiety bearing a peptide backbone.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentCyclic peptides
Alternative Parents
Substituents
  • Aminoglycoside core
  • Cyclic alpha peptide
  • Phenolic glycoside
  • O-glycosyl compound
  • Glycosyl compound
  • Disaccharide
  • Diaryl ether
  • Alpha-amino acid or derivatives
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Amino saccharide
  • Oxane
  • Benzenoid
  • Aryl chloride
  • Aryl halide
  • Cyclic carboximidic acid
  • Secondary alcohol
  • Amino acid
  • 1,2-aminoalcohol
  • Amino acid or derivatives
  • Acetal
  • Oxacycle
  • Carboximidic acid
  • Carboximidic acid derivative
  • Carboxylic acid
  • Azacycle
  • Secondary aliphatic amine
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Ether
  • Propargyl-type 1,3-dipolar organic compound
  • Monocarboxylic acid or derivatives
  • Secondary amine
  • Polyol
  • Organic oxide
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Carbonyl group
  • Primary aliphatic amine
  • Alcohol
  • Organic oxygen compound
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Primary amine
  • Amine
  • Primary alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.25e-01 g/L
LogP-3.1
Predicted Properties
PropertyValueSource
Water Solubility0.23 g/LALOGPS
logP1.11ALOGPS
logP-4.4ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)2.99ChemAxon
pKa (Strongest Basic)9.93ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count24ChemAxon
Hydrogen Donor Count19ChemAxon
Polar Surface Area530.49 ŲChemAxon
Rotatable Bond Count13ChemAxon
Refractivity346.61 m³·mol⁻¹ChemAxon
Polarizability138.7 ųChemAxon
Number of Rings10ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-Ion Trap , Positivesplash10-00di-2901000023-e1b4c2a4d54a44d851b1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - DI-ESI-Hybrid FT , Positivesplash10-00di-2901000023-e1b4c2a4d54a44d851b1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f8c-1923700000-67a86ecb329876118249View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0ufu-2921000000-029bb9d69d210833797cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-8920000000-971cf434a71ef3cbb223View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0h0d-2823900000-fe4b7f6b1b8574952eaaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ox-3911100000-0b893eaecbca11b8af4eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03dl-3900000000-03d8e77b98241f93c67dView in MoNA
Toxicity Profile
Route of ExposurePoorly absorbed from gastrointestinal tract, however systemic absorption may occur following IV administration.
Mechanism of ToxicityThe bactericidal action of vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases. Route of Elimination: In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Half Life: Half-life in normal renal patients is approximately 6 hours (range 4 to 11 hours). In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. In anephric patients, the average half-life of elimination is 7.5 days.
Toxicity ValuesLD50: 5000 mg/kg (Oral, Mouse) (6) LD50: 319 mg/kg (Intravenous, Rat) (6) LD50: 400 mg/kg (Intravenous, Mouse) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesVancomycin is indicated for the treatment of serious or severe infections caused by susceptible strains of methicillin-resistant (beta-lactam-resistant) staphylococci.
Minimum Risk LevelNot Available
Health EffectsRenal failure, principally manifested by increased serum creatinine or BUN concentrations, especially in patients administered large doses of vancomycin, has been reported rarely. A few dozen cases of hearing loss associated with vancomycin have been reported. Reversible neutropenia, usually starting 1 week or more after onset of therapy with vancomycin or after a total dosage of more than 25 g, has been reported for several dozen patients.
SymptomsInflammation at the injection site has been reported. During or soon after rapid infusion of vancomycin, patients may develop anaphylactoid reactions, including hypotension, wheezing, dyspnea, urticaria, or pruritus. Rapid infusion may also cause flushing of the upper body ("red neck") or pain and muscle spasm of the chest and back. These reactions usually resolve within 20 minutes but may persist for several hours. Such events are infrequent if vancomycin is given by a slow infusion over 60 minutes. In studies of normal volunteers, infusion-related events did not occur when vancomycin was administered at a rate of 10 mg/min or less.
TreatmentSupportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00512
HMDB IDHMDB14653
PubChem Compound ID14969
ChEMBL IDCHEMBL262777
ChemSpider ID389935
KEGG IDC06689
UniProt IDNot Available
OMIM ID
ChEBI ID28001
BioCyc IDNot Available
CTD IDNot Available
Stitch IDVancomycin
PDB ID1AA5
ACToR IDNot Available
Wikipedia LinkVancomycin
References
Synthesis Reference
  1. Boger DL. Vancomycin, teicoplanin, and ramoplanin: synthetic and mechanistic studies. Med Res Rev. 2001 Sep;21(5):356-81. Pubmed
MSDSLink
General References
  1. Levine DP: Vancomycin: a history. Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S5-12. [16323120 ]
  2. Small PM, Chambers HF: Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users. Antimicrob Agents Chemother. 1990 Jun;34(6):1227-31. [2393284 ]
  3. Gonzalez C, Rubio M, Romero-Vivas J, Gonzalez M, Picazo JJ: Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms. Clin Infect Dis. 1999 Nov;29(5):1171-7. [10524959 ]
  4. Sivagnanam S, Deleu D: Red man syndrome. Crit Care. 2003 Apr;7(2):119-20. Epub 2002 Dec 23. [12720556 ]
  5. Cantu TG, Yamanaka-Yuen NA, Lietman PS: Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis. 1994 Apr;18(4):533-43. [8038306 ]
  6. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  7. Schafer M, Schneider TR, Sheldrick GM: Crystal structure of vancomycin. Structure. 1996 Dec 15;4(12):1509-15. [8994975 ]
  8. RxList: The Internet Drug Index (2009). [Link]
  9. RxList: The Internet Drug Index (2009). [Link]
  10. Schäfer, Martina, Thomas R Schneider, and George M Sheldrick. 1996. Crystal structure of vancomycin. Structure 4, no. 12 (December 15): 1509-1515. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 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. Bernardeau M, Vernoux JP, Henri-Dubernet S, Gueguen M: Safety assessment of dairy microorganisms: the Lactobacillus genus. Int J Food Microbiol. 2008 Sep 1;126(3):278-85. Epub 2007 Aug 22. [17889388 ]
  4. Baddour MM, Abuelkheir MM, Fatani AJ, Bohol MF, Al-Ahdal MN: Molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) isolates from major hospitals in Riyadh, Saudi Arabia. Can J Microbiol. 2007 Aug;53(8):931-6. [17898849 ]
  5. Prere MF, Baron O, Fayet O: Rapid identification of bacteria, mecA and van genes from blood cultures. Pathol Biol (Paris). 2007 Nov;55(8-9):375-7. [17913394 ]