Tmic
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Record Information
Version2.0
Creation Date2009-07-05 03:20:59 UTC
Update Date2014-12-24 20:25:42 UTC
Accession NumberT3D2568
Identification
Common NameCeftriaxone
ClassSmall Molecule
DescriptionCeftriaxone is only found in individuals that have used or taken this drug. It is a broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears. [PubChem]Ceftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.
Compound Type
  • Amide
  • Amine
  • Anti-Bacterial Agent
  • Cephalosporin
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Acantex
Biotrakson
Cefatriaxone
Ceftriaxona
Ceftriaxonum
Ceftriazone
Rocephin
Rocephine
Chemical FormulaC18H18N8O7S3
Average Molecular Mass554.580 g/mol
Monoisotopic Mass554.046 g/mol
CAS Registry Number73384-59-5
IUPAC Name(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-3-{[(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Traditional Nameceftriaxone
SMILES[H][C@]12SCC(CSC3=NC(=O)C(=O)NN3C)=C(N1C(=O)[C@@]2([H])N=C(O)C(=N/OC)\C1=CSC(=N)N1)C(O)=O
InChI IdentifierInChI=1S/C18H18N8O7S3/c1-25-18(22-12(28)13(29)23-25)36-4-6-3-34-15-9(14(30)26(15)10(6)16(31)32)21-11(27)8(24-33-2)7-5-35-17(19)20-7/h5,9,15H,3-4H2,1-2H3,(H2,19,20)(H,21,27)(H,23,29)(H,31,32)/b24-8-/t9-,15-/m1/s1
InChI KeyInChIKey=VAAUVRVFOQPIGI-SPQHTLEESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cephalosporins. Cephalosporins 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 moiety or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentCephalosporins
Alternative Parents
Substituents
  • Cephalosporin
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid or derivatives
  • Aryl thioether
  • 2,4-disubstituted 1,3-thiazole
  • Alkylarylthioether
  • Meta-thiazine
  • 1,2,4-triazine
  • 1,3-thiazol-2-amine
  • Triazine
  • Azole
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Thiazole
  • Amino acid or derivatives
  • Azetidine
  • Carboxamide group
  • Amino acid
  • Secondary carboxylic acid amide
  • Sulfenyl compound
  • Hemithioaminal
  • Thioether
  • Dialkylthioether
  • Azacycle
  • Carboxylic acid derivative
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Organic nitrogen compound
  • Amine
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxide
  • Organic oxygen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organosulfur compound
  • Primary amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceSolid (MSDS, A308).
Experimental Properties
PropertyValue
Melting Point>155°C
Boiling PointNot Available
Solubility1.05e-01 g/L
LogP-1.7
Predicted Properties
PropertyValueSource
Water Solubility0.1 g/LALOGPS
logP-0.01ALOGPS
logP-1.8ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)3.19ChemAxon
pKa (Strongest Basic)4.17ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area208.98 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity128.47 m³·mol⁻¹ChemAxon
Polarizability51.47 ųChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-0924040000-11c1c4ec5dc051494298View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-05fr-9774123000-c094d2c5681b0477a4aaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0apl-3069470000-ea9533b06f6d727b78d9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05mk-6139010000-862d2dcbf27819f7fdaaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0002-9043100000-fbf004668a64dff18475View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4r-5691220000-22e1520a7886282ef024View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4l-4940000000-3a6002666fe076cf5ad8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-160408d1a7b4d7ae1995View in MoNA
Toxicity Profile
Route of ExposureInhalation; dermal or skin contact; ingestion; intravenous (MSDS, A308).
Mechanism of ToxicityCeftriaxone works by inhibiting the mucopeptide synthesis in the bacterial cell wall. The beta-lactam moiety of Ceftriaxone binds to carboxypeptidases, endopeptidases, and transpeptidases in the bacterial cytoplasmic membrane. These enzymes are involved in cell-wall synthesis and cell division. By binding to these enzymes, Ceftriaxone results in the formation of of defective cell walls and cell death.
MetabolismCeftriaxone is eliminated unchanged in the urine by glomerular filtration (60%) and bile (40%) (2). Route of Elimination: Thirty-three percent to 67% of a ceftriaxone dose was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. Half Life: 5.8-8.7 hours
Toxicity ValuesLD50: >10 000 mg/kg (Oral, Rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the treatment of the infections (respiratory, skin, soft tissue, UTI, ENT) caused by S. pneumoniae, H. influenzae, staphylococci, S. pyogenes (group A beta-hemolytic streptococci), E. coli, P. mirabilis, Klebsiella sp, coagulase-negative staph (1).
Minimum Risk LevelNot Available
Health EffectsSome observed adverse reactions ( < 0.1%) include abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, biliary lithiasis, bronchospasm, colitis, dyspepsia, epistaxis, flatulence, gallbladder sludge, glycosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, a decrease in the prothrombin time, renal precipitations, seizures, and serum sickness (RxList, A308).
SymptomsAbdominal pain.
TreatmentIn the case of overdosage, drug concentration would not be reduced by hemodialysis or peritoneal dialysis. There is no specific antidote. Treatment of overdosage should be symptomatic (RxList, A308).
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01212
HMDB IDHMDB15343
PubChem Compound ID5479530
ChEMBL IDCHEMBL161
ChemSpider ID4514885
KEGG IDC06683
UniProt IDNot Available
OMIM ID
ChEBI ID29007
BioCyc IDNot Available
CTD IDNot Available
Stitch IDCeftriaxone
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkCeftriaxone
References
Synthesis Reference

Monguzzi Riccardo, Menaspace Silvano, Anzaghi Piergiorgio, “Process for the preparation of ceftriaxone.” U.S. Patent US5026843, issued November, 1984.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Miolo G, Caffieri S, Levorato L, Imbesi M, Giusti P, Uz T, Manev R, Manev H: Photoisomerization of fluvoxamine generates an isomer that has reduced activity on the 5-hydroxytryptamine transporter and does not affect cell proliferation. Eur J Pharmacol. 2002 Aug 30;450(3):223-9. [12208313 ]
  3. Brittain HG and Florey K. Profiles of Drug Substances, Excipients and Related Methodology. Volume 30. Toronto ON: Elsevier.
  4. The Merck Index (2009). Ceftriaxone. [Link]
  5. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
Molecular Weight:
78805.265 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>30000 uMNot AvailableBindingDB 50049707
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. [15567297 ]
  2. Biegel A, Gebauer S, Hartrodt B, Brandsch M, Neubert K, Thondorf I: Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9. [15974593 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name:
SLC22A11
Uniprot ID:
Q9NSA0
Molecular Weight:
59970.945 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.38 uMNot AvailableBindingDB 50049707
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. [11909604 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.23 uMNot AvailableBindingDB 50049707
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. [11909604 ]
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory4.39 uMNot AvailableBindingDB 50049707
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. [11909604 ]