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Identification
Name Cloxacillin
Accession Number DB01147 (APRD00882, EXPT01068)
Type small molecule
Groups approved
Description

A semi-synthetic antibiotic that is a chlorinated derivative of oxacillin. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Cloxacillin Sodium
Brand names
  • Novo-Cloxin
  • Nu-Cloxi
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Penicillins
CAS number 61-72-3
Weight Average: 435.881
Monoisotopic: 435.065569098
Chemical Formula C19H18ClN3O5S
InChI Key InChIKey=LQOLIRLGBULYKD-JKIFEVAISA-N
InChI
InChI=1S/C19H18ClN3O5S/c1-8-11(12(22-28-8)9-6-4-5-7-10(9)20)15(24)21-13-16(25)23-14(18(26)27)19(2,3)29-17(13)23/h4-7,13-14,17H,1-3H3,(H,21,24)(H,26,27)/t13-,14+,17-/m1/s1
Plain Text
IUPAC Name
(2S,5R,6R)-6-[3-(2-chlorophenyl)-5-methyl-1,2-oxazole-4-amido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2NC(=O)C1=C(C)ON=C1C1=C(Cl)C=CC=C1)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Phenylpropenes
  • Penicillins
  • Polypeptides
  • Cinnamaldehydes
Substructures
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Phenylpropenes
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Isoxazoles
  • Aryl Halides
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Beta Lactams
  • Penicillins
  • Thiazoles
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Cinnamaldehydes
  • Carboxamides and Derivatives
  • Oxazoles
  • Lactams
  • Imines
  • Azetidines
  • Thiazolidines
Pharmacology
Indication Used to treat infections caused by penicillinase-producing staphylococci, including pneumococci, group A beta-hemolytic streptococci, and penicillin G-sensitive and penicillin G-resistant staphylococci.
Pharmacodynamics Cloxacillin is a semisynthetic antibiotic in the same class as penicillin. Cloxacillin is for use against staphylococci that produce beta-lactamase.
Mechanism of action By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, cloxacillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cloxacillin interferes with an autolysin inhibitor.
Absorption Well absorbed from the gastrointestinal tract.
Volume of distribution Not Available
Protein binding 95%
Metabolism
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Oral LD50 in rat and mouse is 5000 mg/kg. Intravenous LD50 in rat is 1660 mg/kg. Symptoms of overdose include wheezing, tightness in the chest, fever, itching, bad cough, blue skin color, fits, and swelling of face, lips, tongue, or throat.
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Apothecon inc div bristol myers squibb
  • Teva pharmaceuticals usa inc
  • Glaxosmithkline
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Powder, for solution Intramuscular
Powder, for solution Intravenous
Powder, for solution Oral
Prices
Unit description Cost Unit
Cloxacillin Sodium 2 g/vial 7.69 USD vial
Cloxacillin Sodium 1 g/vial 5.89 USD vial
Cloxacillin Sodium 500 mg/vial 4.79 USD vial
Apo-Cloxi 500 mg Capsule 0.38 USD capsule
Novo-Cloxin 500 mg Capsule 0.38 USD capsule
Nu-Cloxi 500 mg Capsule 0.38 USD capsule
Apo-Cloxi 250 mg Capsule 0.19 USD capsule
Novo-Cloxin 250 mg Capsule 0.19 USD capsule
Nu-Cloxi 250 mg Capsule 0.19 USD capsule
Apo-Cloxi 25 mg/ml Liquid 0.05 USD ml
Novo-Cloxin 25 mg/ml Liquid 0.05 USD ml
Nu-Cloxi 25 mg/ml Liquid 0.05 USD ml
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility 13.9 mg/L PhysProp
logP 3 PhysProp
pKa 2.78 Various sources
Predicted Properties
Property Value Source
water solubility 5.32e-02 g/l ALOGPS
logP 2.61 ALOGPS
logP 2.30 ChemAxon Molconvert
logS -3.91 ALOGPS
pKa 13.65 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 112.74 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 106.64 ChemAxon Molconvert
polarizability 41.64 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06923 Link_out
PubChem Compound 6098 Link_out
PubChem Substance 46507109 Link_out
ChemSpider 5873 Link_out
ChEBI 3765 Link_out
ChEMBL 3765 Link_out
Therapeutic Targets Database DAP001161 Link_out
PharmGKB PA449059 Link_out
HET CXN Link_out
Drug Product Database 337757 Link_out
Drugs.com http://www.drugs.com/mtm/cloxacillin.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Cloxacillin Link_out
ATC Codes
  • J01CF02
  • J01CF05
  • J01CF01
AHFS Codes
  • 08:12.16.12
PDB Entries
FDA label Not Available
MSDS show (38 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take on an empty stomach.
Targets

1. Penicillin-binding proteins 1A/1B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: Q8XJ01 Link_out
Gene: pbpA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  3. Kleppe G, Yu W, Strominger JL: Penicillin-binding proteins in Bacillus subtilis mutants. Antimicrob Agents Chemother. 1982 Jun;21(6):979-83. Pubmed

2. Beta-lactamase

Pharmacological action: unknown
Actions: inducer

This protein is a serine beta-lactamase with a substrate specificity for cephalosporins

Organism class: bacterial
UniProt ID: P00811 Link_out
Gene: ampC
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  3. Mirelis B, Rivera A, Miro E, Mesa RJ, Navarro F, Coll P: A simple phenotypic method for differentiation between acquired and chromosomal AmpC beta-lactamases in Escherichia coli. Enferm Infecc Microbiol Clin. 2006 Jun-Jul;24(6):370-2. Pubmed
  4. Ruppe E, Bidet P, Verdet C, Arlet G, Bingen E: First detection of the Ambler class C 1 AmpC beta-lactamase in Citrobacter freundii by a new, simple double-disk synergy test. J Clin Microbiol. 2006 Nov;44(11):4204-7. Epub 2006 Sep 13. Pubmed
  5. Guan XZ, Liu YN, Luo YP, She DY, Zhou G, Chen LA, Xu YP: [A new member of CMY type cephalosporinase prevailing in Escherichia coli.] Zhonghua Yi Xue Za Zhi. 2004 Nov 17;84(22):1872-5. Pubmed

3. Penicillin-binding protein 2a

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q8DNB6 Link_out
Gene: pbp2a
SNPs: SNPJam Report Link_out

References:
  1. 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

4. Penicillin-binding protein 2B

Pharmacological action: yes
Actions: inhibitor
Organism class: bacterial
UniProt ID: P0A3M5 Link_out
Gene: penA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. 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

5. Penicillin-binding protein 3

Pharmacological action: yes
Actions: inhibitor
UniProt ID: Q51504 Link_out
Gene: pbpB
SNPs: SNPJam Report Link_out

References:
  1. 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

6. Penicillin-binding protein 5

Pharmacological action: unknown
Actions: inhibitor

Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors (By similarity)

Organism class: bacterial
UniProt ID: P0AEB3 Link_out
Gene: dacA
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C: Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity. Biochemistry. 2010 Sep 21;49(37):8094-104. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: inhibitor

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

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Oligopeptide transporter, kidney isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jariyawat S, Sekine T, Takeda M, Apiwattanakul N, Kanai Y, Sophasan S, Endou H: The interaction and transport of beta-lactam antibiotics with the cloned rat renal organic anion transporter 1. J Pharmacol Exp Ther. 1999 Aug;290(2):672-7. Pubmed
Carriers

1. Serum albumin

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 colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed
  2. Friedman LA, Lewis PJ: The effect of semisynthetic penicillins on the binding of bilirubin by neonatal serum. Br J Clin Pharmacol. 1980 Jan;9(1):61-5. Pubmed
  3. Okore VC: Effect of ascorbic acid on the binding of cloxacillin sodium to bovine serum albumin. Arzneimittelforschung. 1994 May;44(5):671-3. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:46

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.