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Identification
Name Tetracycline
Accession Number DB00759 (APRD00572)
Type small molecule
Groups approved
Description

Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Anhydrotetracycline
  • TC
  • Tetracycline HCl
Brand names
  • Abramycin
  • Abricycline
  • Achromycin
  • Achromycin V
  • Actisite
  • Agromicina
  • Ambramicina
  • Ambramycin
  • Amycin
  • Bio-Tetra
  • Biocycline
  • Bristaciclin
  • Bristaciclina
  • Bristacycline
  • Cefracycline
  • Ciclibion
  • Copharlan
  • Criseociclina
  • Cyclopar
  • Cytome
  • Democracin
  • Deschlorobiomycin
  • Dumocyclin
  • Enterocycline
  • Hostacyclin
  • Lexacycline
  • Limecycline
  • Liquamycin
  • Medocycline
  • Mericycline
  • Micycline
  • Neocycline
  • Oletetrin
  • Omegamycin
  • Orlycycline
  • Panmycin
  • Polycycline
  • Polyotic
  • Purocyclina
  • Resteclin
  • Retet
  • Robitet
  • Roviciclina
  • SK-Tetracycline
  • Solvocin
  • Sumycin
  • TAC
  • Tetra-CO
  • Tetrabon
  • Tetrachel
  • Tetracycl
  • Tetracycline II
  • Tetracyn
  • Tetradecin
  • Tetrafil
  • Tetramed
  • Tetraverine
  • Tetrex
  • Topicycline
  • Tsiklomistsin
  • Tsiklomitsin
  • Veracin
  • Vetacyclinum
Brand name mixtures
  • Delta-Albaplex tablets (Novobiocin sodium + Prednisolone + Tetracycline hydrochloride)
  • Helidac (Metronidazole + Bismuth subsalicylate + tetracycline hydrochloride)
  • Neo Chlor PWR (Neomycin sulfate + Tetracycline hydrochloride)
  • Neo-Chlor (Neomycin sulfate + Tetracycline hydrochloride)
  • Neotetramed PWR (Neomycin sulfate + Tetracycline hydrochloride)
  • P Onytricin P (Calcium D-pantothenate + Menadione sodium bisulfite + Nicotinamide + Tetracycline hydrochloride + Vitamin A + Vitamin B12 + Vitamin B2 + Vitamin B6 + Vitamin D3 + Vitamin E)
Categories
  • Anti-Bacterial Agents
  • Antiprotozoals
  • Tetracyclines
  • Protein Synthesis Inhibitors
CAS number 60-54-8
Weight Average: 444.4346
Monoisotopic: 444.153265754
Chemical Formula C22H24N2O8
InChI Key InChIKey=OFVLGDICTFRJMM-WESIUVDSSA-N
InChI
InChI=1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1
Plain Text
IUPAC Name
(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tetracyclines
Substructures
  • Tetracyclines
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Aromatic compounds
  • Cinnamaldehydes
  • Ketenes and Derivatives
  • Phenyl Esters
  • Enols
  • Ketones
Pharmacology
Indication Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.
Pharmacodynamics Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.
Mechanism of action Tetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.
Absorption Bioavailability is less than 40% when administered via intramuscular injection, 100% intravenously, and 60-80% orally (fasting adults). Food and/or milk reduce GI absorption of oral preparations of tetracycline by 50% or more.
Volume of distribution Not Available
Protein binding 20 - 67% protein bound
Metabolism

Not metabolized
Route of elimination They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
Half life 6-12 hours
Clearance Not Available
Toxicity LD50=808mg/kg (orally in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00294 Tetracycline Pathway SMP00294
Pharmacoeconomics
Manufacturers
  • Heritage pharmaceuticals inc
  • Bristol laboratories inc div bristol myers co
  • Warner chilcott div warner lambert co
  • Pharmacia and upjohn co
  • Solvay pharmaceuticals
  • Wyeth ayerst laboratories
  • Apothecon inc div bristol myers squibb
  • Angus chemical co
  • Pfipharmecs div pfizer inc
  • On site therapeutics inc
  • Shire development inc
  • Lederle laboratories div american cyanamid co
  • Pfizer laboratories div pfizer inc
  • Storz ophthalmics inc sub american cyanamid co
  • Par pharmaceutical
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Ointment Ophthalmic
Tablet Oral
Prices
Unit description Cost Unit
Tetracycline hcl powder 2.14 USD g
Tetracycline powder 1.37 USD g
Tetracycline HCl 500 mg capsule 0.2 USD capsule
Tetracycline HCl 250 mg capsule 0.15 USD capsule
Apo-Tetra 250 mg Capsule 0.07 USD capsule
Patents Not Available
Properties
State solid
Melting point 165oC
Experimental Properties
Property Value Source
water solubility 231 mg/L at 25 oC (SRC PhysProp experimental -- YALKOWSKY,SH & DANNENFELSER,RM (1992)) PhysProp
logP -0.3 PhysProp
logS -3.12 [ADME Research, USCD] PhysProp
pKa 3.3 Various sources
Predicted Properties
Property Value Source
water solubility 1.33e+00 g/l ALOGPS
logP -0.56 ALOGPS
logP -3.65 ChemAxon Molconvert
logS -2.52 ALOGPS
pKa 4.79 ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 6 ChemAxon Molconvert
polar surface area 181.62 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 114.19 ChemAxon Molconvert
polarizability 43.03 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Link
  2. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed
External Links
Resource Link
KEGG Drug D00201 Link_out
KEGG Compound C06570 Link_out
PubChem Compound 5280962 Link_out
PubChem Substance 46506693 Link_out
ChemSpider 4510286 Link_out
ChEBI 27902 Link_out
ChEMBL 27902 Link_out
Therapeutic Targets Database DAP001527 Link_out
PharmGKB PA451640 Link_out
HET ATC Link_out
Drug Product Database 527777 Link_out
RxList http://www.rxlist.com/cgi/generic2/tetcycl2.htm Link_out
Drugs.com http://www.drugs.com/tetracycline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tetracycline Link_out
ATC Codes
  • A01AB13
  • D06AA04
  • J01AA07
  • S01AA09
  • S02AA08
  • S03AA02
  • A01AB21
  • S01AA02
  • J01AA06
  • J01AA09
  • S01AA04
  • G01AA07
  • D06AA02
  • D06AA03
  • J01AA03
AHFS Codes
  • 08:12.24
  • 52:04.04
PDB Entries
FDA label Not Available
MSDS show (73.8 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminium salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.
Targets

1. 30S ribosomal protein S7

Pharmacological action: yes
Actions: inhibitor
UniProt ID: P02359 Link_out
Gene: rpsG
SNPs: SNPJam Report Link_out

References:
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

2. 30S ribosomal protein S14

Pharmacological action: yes
Actions: inhibitor

Binds 16S rRNA, required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site

Organism class: bacterial
UniProt ID: P0AG59 Link_out
Gene: rpsN Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

3. 30S ribosomal protein S3

Pharmacological action: yes
Actions: inhibitor
UniProt ID: P0A7V3 Link_out
Gene: rpsC
SNPs: SNPJam Report Link_out

References:
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

4. 30S ribosomal protein S8

Pharmacological action: yes
Actions: inhibitor
UniProt ID: P0A7W7 Link_out
Gene: rpsH
SNPs: SNPJam Report Link_out

References:
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

5. 30S ribosomal protein S19

Pharmacological action: yes
Actions: inhibitor

Protein S19 forms a complex with S13 that binds strongly to the 16S ribosomal RNA. Contacts the A site tRNA

Organism class: bacterial
UniProt ID: P0A7U3 Link_out
Gene: rpsS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

6. 16S rRNA

Pharmacological action: yes
Actions: inhibitor

In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.

Gene Sequence: FASTA

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. Nawaz M, Sung K, Khan SA, Khan AA, Steele R: Biochemical and molecular characterization of tetracycline-resistant Aeromonas veronii isolates from catfish. Appl Environ Microbiol. 2006 Oct;72(10):6461-6. Pubmed
  4. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. Pubmed
  5. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. Pubmed
  6. Rasmussen B, Noller HF, Daubresse G, Oliva B, Misulovin Z, Rothstein DM, Ellestad GA, Gluzman Y, Tally FP, Chopra I: Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome. Antimicrob Agents Chemother. 1991 Nov;35(11):2306-11. Pubmed

7. Major prion protein

Pharmacological action: unknown
Actions: inhibitor

The physiological function of PrP is not known

Organism class: human
UniProt ID: P04156 Link_out
Gene: PRNP Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. De Luigi A, Colombo L, Diomede L, Capobianco R, Mangieri M, Miccolo C, Limido L, Forloni G, Tagliavini F, Salmona M: The efficacy of tetracyclines in peripheral and intracerebral prion infection. PLoS One. 2008 Mar 26;3(3):e1888. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. 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. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

2. Solute carrier family 22 member 8

Actions: inhibitor

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)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

4. Solute carrier family 22 member 7

Actions: inhibitor

Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha- ketoglutarate

UniProt ID: Q9Y694 Link_out
Gene: SLC22A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. 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
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:42

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.