DrugBank: Cefoxitin (DB01331)

targets (12) enzymes (1)

Identification

Name

Cefoxitin

Accession Number

DB01331 (EXPT00897)

Type

small molecule

Groups

approved

Description

Cefoxitin is a semi-synthetic, broad-spectrum cepha antibiotic for intravenous administration. It is derived from cephamycin C, which is produced by Streptomyces lactamdurans.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Mefoxin
Mefoxitin

Brand name mixtures

Not Available

Categories

Anti-Bacterial Agents
Antibacterial Agents
Cephalosporins

CAS number

35607-66-0

Weight

Average: 427.452
Monoisotopic: 427.050791293

Chemical Formula

C₁₆H₁₇N₃O₇S₂

InChI Key

InChIKey=WZOZEZRFJCJXNZ-ZBFHGGJFSA-N

InChI

InChI=1S/C16H17N3O7S2/c1-25-16(18-10(20)5-9-3-2-4-27-9)13(23)19-11(12(21)22)8(6-26-15(17)24)7-28-14(16)19/h2-4,14H,5-7H2,1H3,(H2,17,24)(H,18,20)(H,21,22)/t14-,16+/m1/s1

Plain Text

IUPAC Name

(6R,7S)-3-[(carbamoyloxy)methyl]-7-methoxy-8-oxo-7-[2-(thiophen-2-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

SMILES

[H][C@]12SCC(COC(N)=O)=C(N1C(=O)[C@]2(NC(=O)CC1=CC=CS1)OC)C(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Carbamates and Derivatives
Carboxylic Acids and Derivatives
Polypeptides
Cephalosporins

Substructures

Hydroxy Compounds
Acetates
Carbamates and Derivatives
Amino Ketones
Carboxylic Acids and Derivatives
Ethers
Aliphatic and Aryl Amines
Aminals and Derivatives
Beta Lactams
Enamines
Polypeptides
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Cephalosporins
Amino Acids
Lactams
Azetidines
Thiophenes

Pharmacology

Indication

For the treatment of serious infections caused by susceptible strains microorganisms.

Pharmacodynamics

Cefoxitin is a cephamycin antibiotic often grouped with the second-generation cephalosporins. It is active against a broad range of gram-negative bacteria including anaerobes. The methoxy group in the 7a position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.

Mechanism of action

The bactericidal action of cefoxitin results from inhibition of cell wall synthesis.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Minimal (approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period).

Route of elimination

Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile.

Half life

The half-life after an intravenous dose is 41 to 59 minutes.

Clearance

Not Available

Toxicity

The acute intravenous LD50 in the adult female mouse and rabbit was about 8.0 g/kg and greater than 1.0 g/kg, respectively. The acute intraperitoneal LD50 in the adult rat was greater than 10.0 g/kg.

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Acs dobfar spa
App pharmaceuticals llc
Baxter healthcare corp anesthesia and critical care
Hikma farmaceutica (portugal) sa
Orchid healthcare
B braun medical inc
Bioniche pharma usa llc
Merck and co inc

Packagers

Dosage forms

Form	Route	Strength
Powder, for solution	Intramuscular
Powder, for solution	Intravenous

Prices

Unit description	Cost	Unit
Cefoxitin 10 gm vial	112.25 USD	vial
Cefoxitin 2 gm vial	26.28 USD	vial
Cefoxitin 2 gm piggyback bag	22.56 USD	each
Cefoxitin 1 gm vial	13.12 USD	vial
Cefoxitin 1 gm piggyback bag	12.3 USD	each

Patents

Not Available

Properties

State

solid

Melting point

Boiling Pt : 149.5 oC

Experimental Properties

Property	Value	Source
logP	-0.02 [SANGSTER (1993)]	PhysProp

Predicted Properties

Property	Value	Source
water solubility	1.95e-01 g/l	ALOGPS
logP	0.22	ALOGPS
logP	0.29	ChemAxon Molconvert
logS	-3.34	ALOGPS
pKa	10.97	ChemAxon Molconvert
hydrogen acceptor count	6	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	148.26	ChemAxon Molconvert
rotatable bond count	8	ChemAxon Molconvert
refractivity	98.76	ChemAxon Molconvert
polarizability	39.46	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D02345
KEGG Compound	C06887
PubChem Compound	441199
PubChem Substance	46505845
ChemSpider	389981
ChEBI	209807
ChEMBL	209807
Therapeutic Targets Database	DAP000452
PharmGKB	PA448856
Drug Product Database	2128187
RxList	http://www.rxlist.com/cgi/generic/cefoxitin.htm
Drugs.com	http://www.drugs.com/cdi/cefoxitin.html
Wikipedia	http://en.wikipedia.org/wiki/Cefoxitin

ATC Codes

J01DC01

AHFS Codes

08:12.07.12

PDB Entries

1I2W

FDA label

show (76.5 KB)

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. D-alanyl-D-alanine carboxypeptidase dacC Pharmacological action: yes Actions: inhibitor Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors Organism class: bacterial UniProt ID: P08506 Gene: dacC Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 2. Penicillin-binding protein 5 precursor Pharmacological action: yes Actions: inhibitor Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors Organism class: bacterial UniProt ID: P0AEB2 Gene: dacA Protein Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 3. Penicillin-binding protein 7 Pharmacological action: yes Actions: inhibitor UniProt ID: P0AFI5 Gene: pbpG SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 4. Penicillin-binding protein 4 Pharmacological action: yes Actions: inhibitor Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction Organism class: bacterial UniProt ID: P24228 Gene: dacB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 5. Penicillin-binding protein 1A Pharmacological action: yes Actions: inhibitor 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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) Organism class: bacterial UniProt ID: P02918 Gene: mrcA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 6. Penicillin-binding protein 1B Pharmacological action: yes Actions: inhibitor 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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits) Organism class: bacterial UniProt ID: P02919 Gene: mrcB Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 7. Peptidoglycan synthetase ftsI Pharmacological action: yes Actions: inhibitor Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates Organism class: bacterial UniProt ID: P0AD68 Gene: ftsI Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed 8. Penicillin-binding protein 3 Pharmacological action: yes Actions: inhibitor UniProt ID: Q75Y35 Gene: pbp3 SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 9. Penicillin-binding protein 1b Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: Q7CRA4 Gene: pbp1b Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 10. Penicillin-binding protein 2a Pharmacological action: yes Actions: inhibitor UniProt ID: Q8DNB6 Gene: pbp2a SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 11. Penicillin-binding protein 1A Pharmacological action: yes Actions: inhibitor Cell wall formation Organism class: bacterial UniProt ID: Q8DR59 Gene: pbpA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed 12. Penicillin-binding protein 2B Pharmacological action: yes Actions: inhibitor Organism class: bacterial UniProt ID: P0A3M6 Gene: penA Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

Targets

1. D-alanyl-D-alanine carboxypeptidase dacC

Pharmacological action: yes
Actions: inhibitor

Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors

Organism class: bacterial
UniProt ID: P08506 Link_out

Gene: dacC Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

2. Penicillin-binding protein 5 precursor

Pharmacological action: yes
Actions: inhibitor

Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors

Organism class: bacterial
UniProt ID: P0AEB2 Link_out

Gene: dacA
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

3. Penicillin-binding protein 7

Pharmacological action: yes
Actions: inhibitor
UniProt ID: P0AFI5 Link_out

Gene: pbpG
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

4. Penicillin-binding protein 4

Pharmacological action: yes
Actions: inhibitor

Not involved in transpeptidation but exclusively catalyzes a DD-carboxypeptidase and DD-endopeptidase reaction

Organism class: bacterial
UniProt ID: P24228 Link_out

Gene: dacB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

5. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

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 strands) and a penicillin-sensitive transpeptidase C-terminal domain (cross-linking of the peptide subunits)

Organism class: bacterial
UniProt ID: P02918 Link_out

Gene: mrcA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

6. Penicillin-binding protein 1B

Pharmacological action: yes
Actions: inhibitor

Organism class: bacterial
UniProt ID: P02919 Link_out

Gene: mrcB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

7. Peptidoglycan synthetase ftsI

Pharmacological action: yes
Actions: inhibitor

Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates

Organism class: bacterial
UniProt ID: P0AD68 Link_out

Gene: ftsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Matsuhashi M, Tamaki S: Enzymatic studies on the mechanism of action of cefoxitin. Correlation between the affinities of cefoxitin to penicillin-binding proteins and its rates of inhibition of the respective penicillin-sensitive reactions in E. coli. J Antibiot (Tokyo). 1978 Dec;31(12):1292-5. Pubmed

8. Penicillin-binding protein 3

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q75Y35 Link_out

Gene: pbp3
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

9. Penicillin-binding protein 1b

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q7CRA4 Link_out

Gene: pbp1b Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

10. Penicillin-binding protein 2a

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q8DNB6 Link_out

Gene: pbp2a
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

11. Penicillin-binding protein 1A

Pharmacological action: yes
Actions: inhibitor

Cell wall formation

Organism class: bacterial
UniProt ID: Q8DR59 Link_out

Gene: pbpA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

12. Penicillin-binding protein 2B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P0A3M6 Link_out

Gene: penA Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Williamson R, Hakenbeck R, Tomasz A: In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother. 1980 Oct;18(4):629-37. Pubmed

Enzymes
1. Beta-lactamase Actions: substrate A beta-lactam + H(2)O = a substituted beta- amino acid UniProt ID: P00808 Gene: penP Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Song W, Lee KM, Kim HS, Kim JS, Kim J, Jeong SH, Roh KH: Clonal spread of both oxyimino-cephalosporin- and cefoxitin-resistant Klebsiella pneumoniae isolates co-producing SHV-2a and DHA-1 beta-lactamase at a burns intensive care unit. Int J Antimicrob Agents. 2006 Dec;28(6):520-4. Epub 2006 Nov 13. Pubmed d’Azevedo PA, Goncalves AL, Musskopf MI, Ramos CG, Dias CA: Laboratory tests in the detection of extended spectrum beta-lactamase production: National Committee for Clinical Laboratory Standards (NCCLS) screening test, the E-test, the double disk confirmatory test, and cefoxitin susceptibility testing. Braz J Infect Dis. 2004 Oct;8(5):372-7. Epub 2005 Mar 17. Pubmed Ke YY, Lin TH: A theoretical study on the activation of Ser70 in the acylation mechanism of cephalosporin antibiotics. Biophys Chem. 2005 Apr 22;114(2-3):103-13. Epub 2004 Nov 30. Pubmed

Enzymes

1. Beta-lactamase

Actions: substrate

A beta-lactam + H(2)O = a substituted beta- amino acid

UniProt ID: P00808 Link_out

Gene: penP
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Song W, Lee KM, Kim HS, Kim JS, Kim J, Jeong SH, Roh KH: Clonal spread of both oxyimino-cephalosporin- and cefoxitin-resistant Klebsiella pneumoniae isolates co-producing SHV-2a and DHA-1 beta-lactamase at a burns intensive care unit. Int J Antimicrob Agents. 2006 Dec;28(6):520-4. Epub 2006 Nov 13. Pubmed
d’Azevedo PA, Goncalves AL, Musskopf MI, Ramos CG, Dias CA: Laboratory tests in the detection of extended spectrum beta-lactamase production: National Committee for Clinical Laboratory Standards (NCCLS) screening test, the E-test, the double disk confirmatory test, and cefoxitin susceptibility testing. Braz J Infect Dis. 2004 Oct;8(5):372-7. Epub 2005 Mar 17. Pubmed
Ke YY, Lin TH: A theoretical study on the activation of Ser70 in the acylation mechanism of cephalosporin antibiotics. Biophys Chem. 2005 Apr 22;114(2-3):103-13. Epub 2004 Nov 30. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

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.