Identification

Name
Cefmetazole
Accession Number
DB00274  (APRD00852)
Type
Small Molecule
Groups
Approved, Investigational
Description

A semisynthetic cephamycin antibiotic with a broad spectrum of activity against both gram-positive and gram-negative microorganisms. It has a high rate of efficacy in many types of infection and to date no severe side effects have been noted. [PubChem]

Structure
Thumb
Synonyms
  • (6R,7S)-7-({[(cyanomethyl)sulfanyl]acetyl}amino)-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  • Cefmetazolo
  • Cefmetazolum
External IDs
U-72791
Product Ingredients
IngredientUNIICASInChI Key
Cefmetazole sodium37Y9VR4W7A56796-39-5BITQGIOJQWZUPL-UHFFFAOYSA-M
International/Other Brands
Zefazone
Categories
UNII
3J962UJT8H
CAS number
56796-20-4
Weight
Average: 471.534
Monoisotopic: 471.045328759
Chemical Formula
C15H17N7O5S3
InChI Key
SNBUBQHDYVFSQF-HIFRSBDPSA-N
InChI
InChI=1S/C15H17N7O5S3/c1-21-14(18-19-20-21)30-6-8-5-29-13-15(27-2,17-9(23)7-28-4-3-16)12(26)22(13)10(8)11(24)25/h13H,4-7H2,1-2H3,(H,17,23)(H,24,25)/t13-,15+/m1/s1
IUPAC Name
(6R,7S)-7-{2-[(cyanomethyl)sulfanyl]acetamido}-7-methoxy-3-{[(1-methyl-1H-1,2,3,4-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC(CSC3=NN=NN3C)=C(N1C(=O)[[email protected]]2(NC(=O)CSCC#N)OC)C(O)=O

Pharmacology

Indication

For the treatment of infections caused by susceptible organisms.

Structured Indications
Not Available
Pharmacodynamics

Cefmetazole is a second-generation cephalosporin. The cephalosporins are bactericidal drugs with both gram-positive and gram-negative activity. They inhibit bacterial cell wall synthesis in a way similar to the penicillins. Cefmetazole is more active than 1st-generation cephalosporins against indole-positive Proteus, Serratia, anaerobic gram-negative bacilli (including B. fragilis), and some E. coli, Klebsiella, and P. mirabilis, but is less active than cefoxitin or cefotetan against most gram-negative bacilli.

Mechanism of action

The bactericidal activity of cefmetazole results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs).

TargetActionsOrganism
APenicillin binding protein 2a
inhibitor
Staphylococcus aureus
APenicillin-binding protein 1A
inhibitor
Escherichia coli (strain K12)
APenicillin-binding protein 1B
inhibitor
Escherichia coli (strain K12)
APeptidoglycan synthase FtsI
inhibitor
Escherichia coli (strain K12)
AD-alanyl-D-alanine carboxypeptidase DacA
inhibitor
Escherichia coli (strain K12)
AD-alanyl-D-alanine carboxypeptidase DacC
inhibitor
Escherichia coli (strain K12)
Absorption

Bioavailability is approximately 100% following intramuscular injection.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

No appreciable metabolism.

Route of elimination
Not Available
Half life

1.50 ±0.14 hours

Clearance
Not Available
Toxicity

Oral LD50 in rats is 3,204 mg/kg. With other b-lactam antibiotics, adverse effects following overdosage have included nausea, vomiting, epigastric distress, diarrhea, and convulsions.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefmetazole may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefmetazole.Investigational
ClorindioneCefmetazole may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefmetazole may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefmetazole may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefmetazole may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefmetazole may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefmetazole may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefmetazole may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefmetazole.Approved
ProbenecidThe serum concentration of Cefmetazole can be increased when it is combined with Probenecid.Approved
TioclomarolCefmetazole may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefmetazole may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14419
KEGG Drug
D00910
KEGG Compound
C08103
PubChem Compound
42008
PubChem Substance
46504461
ChemSpider
38311
BindingDB
50350471
ChEBI
3489
ChEMBL
CHEMBL1201195
Therapeutic Targets Database
DAP001179
PharmGKB
PA164746819
HET
4KO
Wikipedia
Cefmetazole
ATC Codes
J01DC09 — Cefmetazole
PDB Entries
4kos
MSDS
Download (52.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
3CompletedPreventionNeoplasms, Colorectal1
3CompletedTreatmentSurgery, Colorectal1

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility94.2 mg/LNot Available
logP-0.60SANGSTER (1993)
Predicted Properties
PropertyValueSource
Water Solubility2.16 mg/mLALOGPS
logP-0.38ALOGPS
logP-0.65ChemAxon
logS-2.3ALOGPS
pKa (Strongest Acidic)3.38ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area163.33 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity124.57 m3·mol-1ChemAxon
Polarizability44.5 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8407
Blood Brain Barrier-0.9932
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.8283
P-glycoprotein inhibitor INon-inhibitor0.8047
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8723
CYP450 2C9 substrateNon-substrate0.8274
CYP450 2D6 substrateNon-substrate0.8182
CYP450 3A4 substrateSubstrate0.5951
CYP450 1A2 substrateNon-inhibitor0.8575
CYP450 2C9 inhibitorNon-inhibitor0.82
CYP450 2D6 inhibitorNon-inhibitor0.895
CYP450 2C19 inhibitorNon-inhibitor0.8093
CYP450 3A4 inhibitorNon-inhibitor0.8551
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6417
Ames testNon AMES toxic0.8271
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.9062
Rat acute toxicity2.2638 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9715
hERG inhibition (predictor II)Non-inhibitor0.7599
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Cephems / Alkylarylthioethers / 1,3-thiazines / Tetrazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azetidines / Thiohemiaminal derivatives / Sulfenyl compounds / Azacyclic compounds
show 10 more
Substituents
N-acyl-alpha amino acid or derivatives / Cephem / Aryl thioether / Alkylarylthioether / Meta-thiazine / Azole / Beta-lactam / Heteroaromatic compound / Tertiary carboxylic acid amide / Tetrazole
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:3489)

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Not Available
Gene Name
mecA
Uniprot ID
C1KC03
Uniprot Name
Penicillin binding protein 2a
Molecular Weight
54918.915 Da
References
  1. Yokota T, Yoshida R, Utsui Y, Tajima M: Cefmetazole: a broad spectrum cephem antibiotic effective on methicillin- and cephem-resistant Staphylococcus aureus. Drugs Exp Clin Res. 1985;11(1):29-38. [PubMed:3915273]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcA
Uniprot ID
P02918
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
93635.545 Da
References
  1. de la Rosa EJ, de Pedro MA, Vazquez D: Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5632-5. [PubMed:3898066]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
mrcB
Uniprot ID
P02919
Uniprot Name
Penicillin-binding protein 1B
Molecular Weight
94291.875 Da
References
  1. de la Rosa EJ, de Pedro MA, Vazquez D: Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5632-5. [PubMed:3898066]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Peptidoglycan glycosyltransferase activity
Specific Function
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan fr...
Gene Name
ftsI
Uniprot ID
P0AD68
Uniprot Name
Peptidoglycan synthase FtsI
Molecular Weight
63876.925 Da
References
  1. de la Rosa EJ, de Pedro MA, Vazquez D: Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5632-5. [PubMed:3898066]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Gene Name
dacA
Uniprot ID
P0AEB2
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacA
Molecular Weight
44443.62 Da
References
  1. de la Rosa EJ, de Pedro MA, Vazquez D: Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5632-5. [PubMed:3898066]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors.
Gene Name
dacC
Uniprot ID
P08506
Uniprot Name
D-alanyl-D-alanine carboxypeptidase DacC
Molecular Weight
43608.595 Da
References
  1. de la Rosa EJ, de Pedro MA, Vazquez D: Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5632-5. [PubMed:3898066]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Robertson A, Fink S, Karp W: Effect of cephalosporins on bilirubin-albumin binding. J Pediatr. 1988 Feb;112(2):291-4. [PubMed:3339510]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:35