You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameCefalotin
Accession NumberDB00456  (APRD00859, EXPT00946)
Typesmall molecule
Groupsapproved
Description

A cephalosporin antibiotic. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
CefalothinNot AvailableNot Available
CefalotinaSpanishINN
CefalotineFrenchINN
CefalotinumLatinINN
CephalothinNot AvailableUSAN
CephalotinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Cefalotin Sodium
58-71-9
Thumb
  • InChI Key: VUFGUVLLDPOSBC-XRZFDKQNSA-M
  • Monoisotopic Mass: 418.026922277
  • Average Mass: 418.42
DBSALT000262
Brand names
NameCompany
CoaxinNot Available
KeflinLilly
Brand mixturesNot Available
Categories
CAS number153-61-7
WeightAverage: 396.438
Monoisotopic: 396.044977634
Chemical FormulaC16H16N2O6S2
InChI KeyXIURVHNZVLADCM-IUODEOHRSA-N
InChI
InChI=1S/C16H16N2O6S2/c1-8(19)24-6-9-7-26-15-12(14(21)18(15)13(9)16(22)23)17-11(20)5-10-3-2-4-25-10/h2-4,12,15H,5-7H2,1H3,(H,17,20)(H,22,23)/t12-,15-/m1/s1
IUPAC Name
(6R,7R)-3-[(acetyloxy)methyl]-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(C)=O)=C(N1C(=O)[C@H]2NC(=O)CC1=CC=CS1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactams
SubclassBeta Lactams
Direct parentCephalosporins
Alternative parentsN-acyl-alpha Amino Acids and Derivatives; 1,3-Thiazines; Thiophenes; Tertiary Carboxylic Acid Amides; Azetidines; Secondary Carboxylic Acid Amides; Carboxylic Acid Esters; Tertiary Amines; Hemiaminals; Ethers; Enamines; Carboxylic Acids; Thioethers; Polyamines; Aminals; Enolates
Substituentsn-acyl-alpha amino acid or derivative; meta-thiazine; thiophene; tertiary carboxylic acid amide; tertiary amine; azetidine; hemiaminal; carboxylic acid ester; secondary carboxylic acid amide; carboxamide group; polyamine; thioether; ether; enamine; carboxylic acid; aminal; carboxylic acid derivative; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moeity or a derivative thereof.
Pharmacology
IndicationUsed to prevent infection during surgery and to treat many kinds of infections of the blood, bone or joints, respiratory tract, skin, and urinary tract.
PharmacodynamicsCefalotin (INN) or cephalothin (USAN) is a semisynthetic first generation cephalosporin having a broad spectrum of antibiotic activity that is administered parenterally.
Mechanism of actionThe bactericidal activity of cefalotin results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). The PBPs are transpeptidases which are vital in peptidoglycan biosynthesis. Therefore, their inhibition prevents this vital cell wall compenent from being properly synthesized.
AbsorptionNot Available
Volume of distributionNot Available
Protein binding65-80%
Metabolism

Metabolized to a less active desacetyl metabolite, although 50-75% of the drug is eliminated unchanged in the urine.

Route of eliminationNot Available
Half life30 minutes
ClearanceNot Available
ToxicityRat intravenous LD50 is 4000 mg/kg.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption - 0.8642
Blood Brain Barrier - 0.9956
Caco-2 permeable - 0.8078
P-glycoprotein substrate Substrate 0.8408
P-glycoprotein inhibitor I Non-inhibitor 0.8839
P-glycoprotein inhibitor II Non-inhibitor 0.9724
Renal organic cation transporter Non-inhibitor 0.8758
CYP450 2C9 substrate Non-substrate 0.7675
CYP450 2D6 substrate Non-substrate 0.8299
CYP450 3A4 substrate Non-substrate 0.5
CYP450 1A2 substrate Non-inhibitor 0.8059
CYP450 2C9 substrate Non-inhibitor 0.8379
CYP450 2D6 substrate Non-inhibitor 0.9052
CYP450 2C19 substrate Non-inhibitor 0.8027
CYP450 3A4 substrate Non-inhibitor 0.8938
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7713
Ames test Non AMES toxic 0.7446
Carcinogenicity Non-carcinogens 0.9182
Biodegradation Not ready biodegradable 0.9305
Rat acute toxicity 1.6998 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9882
hERG inhibition (predictor II) Non-inhibitor 0.8883
Pharmacoeconomics
Manufacturers
  • International medication systems ltd
  • Abbott laboratories pharmaceutical products div
  • Abraxis pharmaceutical products
  • Bristol laboratories inc div bristol myers co
  • Baxter healthcare corp
  • Eli lilly and co
  • Glaxosmithkline
PackagersNot Available
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point160-160.5 °CPhysProp
water solubility158 mg/LNot Available
logP0.00HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility5.21e-02 g/lALOGPS
logP0.63ALOGPS
logP0.016ChemAxon
logS-3.9ALOGPS
pKa (strongest acidic)3.63ChemAxon
pKa (strongest basic)-3.3ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count2ChemAxon
polar surface area113.01ChemAxon
rotatable bond count7ChemAxon
refractivity93.79ChemAxon
polarizability37.22ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Michael D. Cise, Michael L. Roy, “Method of preparing a rapidly dissolving powder of crystalline cephalothin sodium for parenteral administration.” U.S. Patent US4132848, issued December, 1977.

US4132848
General ReferenceNot Available
External Links
ResourceLink
KEGG CompoundC07761
PubChem Compound6024
PubChem Substance46509079
ChemSpider5802
ChEBI124991
ChEMBLCHEMBL617
Therapeutic Targets DatabaseDAP000155
PharmGKBPA448886
HETCEO
Drug Product Database2060051
WikipediaCefalotin
ATC CodesJ01DB03
AHFS Codes
  • 08:12.06.04
PDB Entries
FDA labelNot Available
MSDSshow(59.2 KB)
Interactions
Drug Interactions
Drug
AmikacinIncreased risk of nephrotoxicity
Food InteractionsNot Available

Targets

1. D-alanyl-D-alanine carboxypeptidase

Kind: protein

Organism: Streptomyces sp. (strain R61)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
D-alanyl-D-alanine carboxypeptidase P15555 Details

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. Wrezel PW, Ellis LF, Neuhaus FC: In vivo target of benzylpenicillin in Gaffkya homari. Antimicrob Agents Chemother. 1986 Mar;29(3):432-9. Pubmed
  4. Kuzin AP, Liu H, Kelly JA, Knox JR: Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry. 1995 Jul 25;34(29):9532-40. Pubmed
  5. Frere JM, Geurts F, Ghuysen JM: The exocellular DD-carboxypeptidase-endopeptidase of Streptomyces albus G. Interaction with beta-lactam antibiotics. Biochem J. 1978 Dec 1;175(3):801-5. Pubmed

2. Penicillin-binding protein 1A

Kind: protein

Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A Q8DR59 Details

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

3. Penicillin-binding protein 1b

Kind: protein

Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1b Q7CRA4 Details

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 3

Kind: protein

Organism: Streptococcus pneumoniae

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 3 Q75Y35 Details

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 2a

Kind: protein

Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 2a Q8DNB6 Details

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 2B

Kind: protein

Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 2B P0A3M6 Details

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

7. Penicillin-binding protein 1A

Kind: protein

Organism: Clostridium perfringens (strain 13 / Type A)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Penicillin-binding protein 1A Q8XJ01 Details

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. Botta GA, Buffa D: Murein synthesis and beta-lactam antibiotic susceptibility during rod-to-sphere transition in a pbpA(Ts) mutant of Escherichia coli. Antimicrob Agents Chemother. 1981 May;19(5):891-900. Pubmed

8. Beta-lactamase

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: potentiator

Components

Name UniProt ID Details
Beta-lactamase P00811 Details

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. Diaz N, Suarez D, Merz KM Jr, Sordo TL: Molecular dynamics simulations of the TEM-1 beta-lactamase complexed with cephalothin. J Med Chem. 2005 Feb 10;48(3):780-91. Pubmed
  4. Bethel CR, Hujer AM, Hujer KM, Thomson JM, Ruszczycky MW, Anderson VE, Pusztai-Carey M, Taracila M, Helfand MS, Bonomo RA: Role of Asp104 in the SHV beta-lactamase. Antimicrob Agents Chemother. 2006 Dec;50(12):4124-31. Epub 2006 Sep 18. Pubmed
  5. Oelschlaeger P, Mayo SL, Pleiss J: Impact of remote mutations on metallo-beta-lactamase substrate specificity: implications for the evolution of antibiotic resistance. Protein Sci. 2005 Mar;14(3):765-74. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Terasaki T, Nouda H, Tsuji A: Selective analysis of mutual displacement effects at the primary binding sites of phenoxymethylpenicillin and cephalothin bindings to human serum albumin. J Pharmacobiodyn. 1992 Mar;15(3):91-7. Pubmed

Transporters

1. Solute carrier family 22 member 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 5 O76082 Details

References:

  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

2. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

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 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

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

4. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed
  3. 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

5. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed
  2. Jung KY, Takeda M, Shimoda M, Narikawa S, Tojo A, Kim DK, Chairoungdua A, Choi BK, Kusuhara H, Sugiyama Y, Sekine T, Endou H: Involvement of rat organic anion transporter 3 (rOAT3) in cephaloridine-induced nephrotoxicity: in comparison with rOAT1. Life Sci. 2002 Mar 8;70(16):1861-74. Pubmed

6. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Takeda M, Babu E, Narikawa S, Endou H: Interaction of human organic anion transporters with various cephalosporin antibiotics. Eur J Pharmacol. 2002 Mar 8;438(3):137-42. Pubmed

7. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Khamdang S, Takeda M, Babu E, Noshiro R, Onozato ML, Tojo A, Enomoto A, Huang XL, Narikawa S, Anzai N, Piyachaturawat P, Endou H: Interaction of human and rat organic anion transporter 2 with various cephalosporin antibiotics. Eur J Pharmacol. 2003 Mar 28;465(1-2):1-7. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:10