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Showing drug card for Clavulanate (DB00766)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:02
Primary Accession Number DB00766
Secondary Accession Number
  • APRD00049
Name Clavulanate
Drug Type
  • Approved
  • Small Molecule
Description Clavulanic acid and its salts and esters. The acid is a suicide inhibitor of bacterial beta-lactamase enzymes from Streptomyces clavuligerus. Administered alone, it has only weak antibacterial activity against most organisms, but given in combination with beta-lactam antibiotics prevents antibiotic inactivation by microbial lactamase. [PubChem]
Synonyms
  1. Clavulanic Acid
Brand Names Not Available
Brand Mixtures
  1. Amoksiklav (potassium clavulanate + amoxicillin)
  2. Augmentin (potassium clavulanate + amoxicillin)
  3. Ciblor (potassium clavulanate + amoxicillin)
  4. Klavocin (potassium clavulanate + amoxicillin)
  5. Neo-Duplamox (potassium clavulanate + amoxicillin)
Chemical IUPAC Name (2R,3Z,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Chemical Formula C8H9NO5
Chemical Structure Structure
CAS Registry Number 58001-44-8
InChI Identifier InChI=1/C8H9NO5/c10-2-1-4-7(8(12)13)9-5(11)3-6(9)14-4/h1,6-7,10H,2-3H2,(H,12,13)/b4-1-/t6-,7-/m1/s1/f/h12H
InChI Key HZZVJAQRINQKSD-UFPVBIFCDT
KEGG Drug Not Available
KEGG Compound C06662 Link Image
PubChem Compound 5280980 Link Image
PubChem Substance 8887 Link Image
ChEBI ID 3736 Link Image
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Clavulanate Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference M. Cole et al.; Ger. Pat. 2,517,316(1975)
Average Molecular Weight 199.1608
Monoisotopic Molecular Weight 199.0481
State Solid
Melting Point 117.5-118 oC
Experimental Water Solubility 300 mg/mL (potassium salt) Source: PhysProp
Predicted Water Solubility 3.37e+02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.5 Source: PhysProp
Predicted LogP -1.16 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS 0.23 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID 3BLM Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES OC\C=C1/O[C@@H]2CC(=O)N2[C@H]1C(O)=O
Canonical SMILES OCC=C1OC2CC(=O)N2C1C(O)=O
Drug Category
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
ATC Codes Not Available
AHFS Codes Not Available
Indication For use with Amoxicillin, clavulanic acid is suitable for the treatment of infections with Staph. aureus and Bacteroides fragilis, or with beta-lactamase producing H. influenzae and E. coli.
Pharmacology Clavulanic acid, produced by the fermentation of Streptomyces Clavuligerus, is a beta-lactam structurally related to the penicillins. Clavulanic acid is used in conjunction with amoxicillin for the treatment of bronchitis and urinary tract, skin, and soft tissue infections caused by beta-lactamase producing organisms.
Mechanism of Action Clavulanic acid competitively and irreversibly inhibits a wide variety of beta-lactamases, commonly found in microorganisms resistant to penicillins and cephalosporins. By inactivating beta-lactamase (the bacterial resistance protein), the accompanying penicillin/cephalosporin drugs may be made more potent.
Absorption 75%
Toxicity Gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients
Protein Binding Low (22 to 30%)
Biotransformation Hepatic
Half Life 1.0 hour
Dosage Forms Not Available
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Demeclocycline Possible antagonism of action
Doxycycline Possible antagonism of action
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Methacycline Possible antagonism of action
Methotrexate The penicillin increases the effect and toxicity of methotrexate
Minocycline Possible antagonism of action
Oxytetracycline Possible antagonism of action
Rolitetracycline Possible antagonism of action
Tetracycline Possible antagonism of action
Food Interactions Not Available
Pathways Not Available
General References
  1. Wikipedia Link Image
Organisms Affected
  • Enteric bacteria and other eubacteria
Targets
  1. Beta-lactamase
Drug Target 1 [top]
Target 1 ID 332
Target 1 Name Beta-lactamase
Target 1 Synonyms
  1. Beta-lactamase precursor
  2. EC 3.5.2.6
  3. Penicillinase
Target 1 Gene Name blaZ
Target 1 Protein Sequence >Beta-lactamase precursor 
MKKLIFLIVIALVLSACNSNSSHAKELNDLEKKYNAHIGVYALDTKSGKEVKFNSDKRFA
YASTSKAINSAILLEQVPYNKLNKKVHINKDDIVAYSPILEKYVGKDITLKALIEASMTY
SDNTANNKIIKEIGGIKKVKQRLKELGDKVTNPVRYEIELNYYSPKSKKDTSTPAAFGKT
LNKLIANGKLSKENKKFLLDLMLNNKSGDTLIKDGVPKDYKVADKSGQAITYASRNDVAF
VYPKGQSEPIVLVIFTNKDNKSDKPNDKLISETAKSVMKEF
Target 1 Number of Residues 285
Target 1 Molecular Weight 31350
Target 1 Theoretical pI 10.15
Target 1 GO Classification
Function
catalytic activity
hydrolase activity
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides
beta-lactamase activity
Process
physiological process
metabolism
cellular metabolism
drug metabolism
antibiotic metabolism
antibiotic catabolism
beta-lactam antibiotic catabolism
response to stimulus
response to abiotic stimulus
response to chemical stimulus
response to drug
response to antibiotic
Component
Not Available
Target 1 General Function Involved in antibiotic degradation
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
Penicillins and cephalosporins biosynthesis map00311 Link Image
Target 1 Reactions
  • a beta-lactam + H2O = a substituted beta-amino acid
Target 1 Pfam Domain Function
Target 1 Signals
  • 1-24
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 581568 Link Image
Target 1 UniProtKB/Swiss-Prot ID P00807 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name BLAC_STAAU Link Image
Target 1 PDB ID 3BLM Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >846 bp 
TTGAAAAAGTTAATATTTTTAATTGTAATTGCTTTAGTTTTAAGTGCATGTAATTCAAAC
AGTTCACATGCCAAAGAGTTAAATGATTTAGAAAAAAAATATAATGCTCATATTGGTGTT
TATGCTTTAGATACTAAAAGTGGTAAGGAAGTAAAATTTAATTCAGATAAGAGATTTGCC
TATGCTTCAACTTCAAAAGCGATAAATAGTGCTATTTTGTTAGAACAAGTACCTTATAAT
AAGTTAAATAAAAAAGTACATATTAACAAAGATGATATAGTTGCTTATTCTCCTATTTTA
GAAAAATATGTAGGAAAAGATATCACTTTAAAAGCACTTATTGAGGCTTCAATGACATAT
AGTGATAATACAGCAAACAATAAAATTATAAAAGAAATCGGTGGAATCAAAAAAGTTAAA
CAACGTCTAAAAGAACTAGGAGATAAAGTAACAAATCCAGTTAGATATGAGATAGAATTA
AATTACTATTCACCAAAGAGCAAAAAAGATACTTCAACACCTGCTGCCTTCGGTAAGACC
CTTAATAAACTTATCGCCAATGGAAAATTAAGCAAAGAAAACAAAAAATTCTTACTTGAT
TTAATGTTAAATAATAAAAGCGGAGATACTTTAATTAAAGACGGTGTTCCAAAAGACTAT
AAGGTTGCTGATAAAAGTGGTCAAGCAATAACATATGCTTCTAGAAATGATGTTGCTTTT
GTTTATCCTAAGGGCCAATCTGAACCTATTGTTTTAGTCATTTTTACGAATAAAGACAAT
AAAAGTGATAAGCCAAATGATAAGTTGATAAGTGAAACCGCCAAGAGTGTAATGAAGGAA
TTTTAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Chen CC, Herzberg O: Relocation of the catalytic carboxylate group in class A beta-lactamase: the structure and function of the mutant enzyme Glu166-->Gln:Asn170-->Asp. Protein Eng. 1999 Jul;12(7):573-9. [PubMed Link Image]
  2. Ambler RP: The amino acid sequence of Staphylococcus aureus penicillinase. Biochem J. 1975 Nov;151(2):197-218. [PubMed Link Image]
  3. Herzberg O: Refined crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.0 A resolution. J Mol Biol. 1991 Feb 20;217(4):701-19. [PubMed Link Image]
  4. Rowland SJ, Dyke KG: Tn552, a novel transposable element from Staphylococcus aureus. Mol Microbiol. 1990 Jun;4(6):961-75. [PubMed Link Image]
  5. Gillespie MT, Skurray RA: Nucleotide sequence of the blaZ gene of the Staphylococcus aureus beta-lactamase transposon Tn4002. Nucleic Acids Res. 1989 Nov 11;17(21):8854. [PubMed Link Image]
  6. Wang PZ, Novick RP: Nucleotide sequence and expression of the beta-lactamase gene from Staphylococcus aureus plasmid pI258 in Escherichia coli, Bacillus subtilis, and Staphylococcus aureus. J Bacteriol. 1987 Apr;169(4):1763-6. [PubMed Link Image]
  7. Herzberg O, Moult J: Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution. Science. 1987 May 8;236(4802):694-701. [PubMed Link Image]
  8. Chan PT: Nucleotide sequence of the Staphylococcus aureus PC1 beta-lactamase gene. Nucleic Acids Res. 1986 Jul 25;14(14):5940. [PubMed Link Image]
  9. McLaughlin JR, Murray CL, Rabinowitz JC: Unique features in the ribosome binding site sequence of the gram-positive Staphylococcus aureus beta-lactamase gene. J Biol Chem. 1981 Nov 10;256(21):11283-91. [PubMed Link Image]
  10. Banerjee S, Pieper U, Kapadia G, Pannell LK, Herzberg O: Role of the omega-loop in the activity, substrate specificity, and structure of class A beta-lactamase. Biochemistry. 1998 Mar 10;37(10):3286-96. [PubMed Link Image]
Target 1 Drug References
  1. Poirel L, Brinas L, Verlinde A, Ide L, Nordmann P: BEL-1, a novel clavulanic acid-inhibited extended-spectrum beta-lactamase, and the class 1 integron In120 in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2005 Sep;49(9):3743-8. [PubMed Link Image]
  2. Pottumarthy S, Sader HS, Fritsche TR, Jones RN: Susceptibility patterns for amoxicillin/clavulanate tests mimicking the licensed formulations and pharmacokinetic relationships: do the MIC obtained with 2:1 ratio testing accurately reflect activity against beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis? Diagn Microbiol Infect Dis. 2005 Nov;53(3):225-31. Epub 2005 Oct 27. [PubMed Link Image]
  3. 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. [PubMed Link Image]
  4. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
  5. Hugonnet JE, Blanchard JS: Irreversible Inhibition of the Mycobacterium tuberculosis beta-Lactamase by Clavulanate. Biochemistry. 2007 Oct 4;. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.