T3DB: Ceftriaxone

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2009-07-05 03:20:59 UTC

Update Date

2014-12-24 20:25:42 UTC

Accession Number

T3D2568

Identification

Common Name

Ceftriaxone

Class

Small Molecule

Description

Ceftriaxone 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

MOL SDF PDB SMILES InChI

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 Formula

C₁₈H₁₈N₈O₇S₃

Average Molecular Mass

554.580 g/mol

Monoisotopic Mass

554.046 g/mol

CAS Registry Number

73384-59-5

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 Name

ceftriaxone

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 Identifier

InChI=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 Key

InChIKey=VAAUVRVFOQPIGI-SPQHTLEESA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Carbohydrates and carbohydrate conjugates

Direct Parent

Aminoglycosides

Alternative Parents

Substituents

Aminoglycoside core
Macrolide
Glycosyl compound
O-glycosyl compound
Oxane
Monosaccharide
Tertiary alcohol
1,2-aminoalcohol
Amino acid or derivatives
Carboxylic acid ester
Ketone
Cyclic ketone
Tertiary aliphatic amine
Tertiary amine
Secondary alcohol
Lactone
Acetal
Carboxylic acid derivative
Dialkyl ether
Ether
Oxacycle
Organoheterocyclic compound
Monocarboxylic acid or derivatives
Organic nitrogen compound
Carbonyl group
Hydrocarbon derivative
Alcohol
Amine
Organopnictogen compound
Organonitrogen compound
Organic oxide
Aliphatic heteromonocyclic compound

Molecular Framework

Aliphatic heteromonocyclic compounds

External Descriptors

macrolide antibiotic (CHEBI:3732 )
Macrolides and lactone polyketides (C06912 )
Macrolides and lactone polyketides (LMPK04000014 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

antibacterial drug

Biological Roles

Chemical Roles

EC 3.5.2.6 (beta-lactamase) inhibitor

Physical Properties

State

Solid

Appearance

Solid (MSDS, A308).

Experimental Properties

Property	Value
Melting Point	>155°C
Boiling Point	Not Available
Solubility	1.05e-01 g/L
LogP	-1.7

Predicted Properties

Property	Value	Source
Water Solubility	0.1 g/L	ALOGPS
logP	-0.01	ALOGPS
logP	-1.8	ChemAxon
logS	-3.7	ALOGPS
pKa (Strongest Acidic)	3.19	ChemAxon
pKa (Strongest Basic)	4.17	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	208.98 Å²	ChemAxon
Rotatable Bond Count	8	ChemAxon
Refractivity	128.47 m³·mol⁻¹	ChemAxon
Polarizability	51.47 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-0924040000-11c1c4ec5dc051494298	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-05fr-9774123000-c094d2c5681b0477a4aa	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS ("Ceftriaxone,1TMS,#1" TMS) - 70eV, Positive	Not Available	2021-10-14	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_2) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_3) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TMS_1_4) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_1) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_2) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_3) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (TBDMS_1_4) - 70eV, Positive	Not Available	2021-10-15	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0apl-3069470000-ea9533b06f6d727b78d9	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-05mk-6139010000-862d2dcbf27819f7fdaa	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0002-9043100000-fbf004668a64dff18475	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4r-5691220000-22e1520a7886282ef024	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4l-4940000000-3a6002666fe076cf5ad8	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-160408d1a7b4d7ae1995	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0a4i-0013090000-bb4e8b82e0fb04e55aad	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0avi-0466190000-080d962933aef409d2d1	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-056u-1944420000-18694b9d401854bf9e80	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0pb9-0910080000-bcb5ef0d6c356695310e	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-0900000000-803717215c9d04868fa4	2021-10-11	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9400000000-75fd909b2cc72f5d0010	2021-10-11	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum

Toxicity Profile

Route of Exposure

Inhalation; dermal or skin contact; ingestion; intravenous (MSDS, A308).

Mechanism of Toxicity

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.

Metabolism

Ceftriaxone 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 Values

LD50: >10 000 mg/kg (Oral, Rat)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

For 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 Level

Not Available

Health Effects

Some 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).

Symptoms

Abdominal pain.

Treatment

In 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

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

29007

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Ceftriaxone

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Ceftriaxone

References

Synthesis Reference

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

MSDS

Link

General References

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 ]
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 ]
Brittain HG and Florey K. Profiles of Drug Substances, Excipients and Related Methodology. Volume 30. Toronto ON: Elsevier.
The Merck Index (2009). Ceftriaxone. [Link]
Drugs.com [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Solute carrier family 15 member 1

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

Type	Value	Assay Type	Assay Source
Inhibitory	>30000 uM	Not Available	BindingDB 50049707

References

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 ]
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 ]

Target Details

2. Solute carrier family 22 member 11

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

Type	Value	Assay Type	Assay Source
Inhibitory	2.38 uM	Not Available	BindingDB 50049707

References

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 ]

Target Details

3. Solute carrier family 22 member 6

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

Type	Value	Assay Type	Assay Source
Inhibitory	0.23 uM	Not Available	BindingDB 50049707

References

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 ]

Target Details

4. Solute carrier family 22 member 8

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

Type	Value	Assay Type	Assay Source
Inhibitory	4.39 uM	Not Available	BindingDB 50049707

References

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 ]

Ceftriaxone (T3D2568)

Structure for T3D2568: Ceftriaxone

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References