Tmic
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Record Information
Version2.0
Creation Date2014-08-28 21:19:25 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3955
Identification
Common NameTetracycline
ClassSmall Molecule
DescriptionTetracycline 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.
Compound Type
  • Anti-Bacterial Agent
  • Antiprotozoal Agent
  • Drug
  • Metabolite
  • Organic Compound
  • Protein Synthesis Inhibitor
  • Synthetic Compound
  • Tetracycline
Chemical Structure
Thumb
Synonyms
Synonym
(4S,4AS,5as,12as)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide
Abramycin
Achromycin
Anhydrotetracycline
Deschlorobiomycin
Liquamycin
Tetracyclin
TETRACYCLINE
Tetracycline HCl
Tetracyclinum
Tetrazyklin
Tsiklomitsin
Chemical FormulaC22H24N2O8
Average Molecular Mass444.435 g/mol
Monoisotopic Mass444.153 g/mol
CAS Registry Number60-54-8
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
Traditional Nametetracycline
SMILES[H][C@]12C[C@@]3([H])[C@]([H])(N(C)C)C(O)=C(C(O)=N)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C(C=CC=C1O)[C@@]2(C)O
InChI IdentifierInChI=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
InChI KeyInChIKey=OFVLGDICTFRJMM-WESIUVDSSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassTetracyclines
Sub ClassNot Available
Direct ParentTetracyclines
Alternative Parents
Substituents
  • Tetracycline
  • Naphthacene
  • Tetracene
  • Anthracene carboxylic acid or derivatives
  • Tetralin
  • Aryl ketone
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Cyclohexenone
  • Aralkylamine
  • Benzenoid
  • Tertiary alcohol
  • Vinylogous acid
  • Tertiary aliphatic amine
  • Amino acid or derivatives
  • Tertiary amine
  • Carboxamide group
  • Primary carboxylic acid amide
  • Ketone
  • Polyol
  • Carboxylic acid derivative
  • Enol
  • Amine
  • Organic oxygen compound
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Alcohol
  • Carbonyl group
  • Organic nitrogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Bone Marrow
  • Heart
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Tetracycline Action PathwaySMP00294 Not Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point172.5 dec°C
Boiling PointNot Available
Solubility231 mg/L (at 25°C)
LogP-1.3
Predicted Properties
PropertyValueSource
Water Solubility1.33 g/LALOGPS
logP-0.56ALOGPS
logP-3.5ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)-2.2ChemAxon
pKa (Strongest Basic)8.24ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area181.62 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity114.19 m³·mol⁻¹ChemAxon
Polarizability43.03 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
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, Positivesplash10-0bvi-5259500000-bd5eacef407c7cbcfc2aView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0002-5023749000-5781179b3d4ec0f18e56View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01sc-1900000000-7b792268aeb0a63c32c5View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-01p9-1900000000-da0b69e206bb0369723cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-000i-3900000000-299e4496b1f8e2f213ccView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01ta-0000900000-e5ca6594fe72eb2bcd1fView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ik9-0402900000-9ef4a0d08180ce9b2a1cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004j-0000900000-b0b8239482dc0ab660e1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01t9-0001900000-11d8380f89252d777068View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0btc-2268900000-9b20bc13399f86c0ff4aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0002900000-bbde63c16f1d6207b45aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0fal-0118900000-1d65f8ee8fa0af312c20View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00r6-9166000000-84828062c581777db668View in MoNA
Toxicity Profile
Route of ExposureBioavailability 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.
Mechanism of ToxicityTetracyclines target the 28S small subunit of the mitochondrial ribosome thereby deactivation mitochondrial protein synthesis. As a result tetracyclines are cytotoxic to the most metabolically active cells or tissues including the heart, liver, thymus and bone-marrow. (2). The likely target of most tetracyclines is the 12S rRNA molecule in the mitochondrial ribosome, which is analogous to the 16S rRNA in bacterial ribosomes.
MetabolismNot 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
Toxicity ValuesLD50=808mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed 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.
Minimum Risk LevelNot Available
Health EffectsSide effects from normal doses of tetracyclines are relatively minimal, but of particular note is phototoxicity. Tetracylclines increase the risk of sunburn under exposure to light from the sun or other sources. Tetracyclines may also cause stomach or bowel upsets, and, on rare occasions, allergic reactions. Very rarely, severe headache and vision problems may be signs of dangerous secondary intracranial hypertension, also known as pseudotumor cerebri. Tetracyclines are teratogens and cause tooth discolouration and poor tooth mineralization in the fetus as they develop in infancy. Symptoms of tetracycline overdose include anorexia, nausea, diarrhea, glossitis, dysphagia, enterocolitis and inflammatory lesions, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia.
SymptomsNot Available
TreatmentDrug therapy is discontinued immediately; exchange transfusion may be required to remove the drug. Sometimes, phenobarbital (UGT induction) is used.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00759
HMDB IDHMDB14897
PubChem Compound ID5280962
ChEMBL IDCHEMBL1440
ChemSpider ID4510286
KEGG IDC06570
UniProt IDNot Available
OMIM ID
ChEBI ID27902
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTetracycline
References
Synthesis Reference

Thomas F. McNamara, Nungavaram S. Ramamurthy, Lorne M. Golub, “Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same.” U.S. Patent US4704383, issued May, 1963.

MSDSLink
General References
  1. 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. doi: 10.1152/ajpcell.00047.2010. Epub 2010 Jun 30. [20592239 ]
  2. McKee EE, Ferguson M, Bentley AT, Marks TA: Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones. Antimicrob Agents Chemother. 2006 Jun;50(6):2042-9. [16723564 ]
  3. Wikipedia. Tetracycline. Last updated on 29 July 2014. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Tubulin binding
Specific Function:
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Gene Name:
PRNP
Uniprot ID:
P04156
Molecular Weight:
27661.21 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  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. doi: 10.1371/journal.pone.0001888. [18365024 ]
  3. Tagliavini F, Forloni G, Colombo L, Rossi G, Girola L, Canciani B, Angeretti N, Giampaolo L, Peressini E, Awan T, De Gioia L, Ragg E, Bugiani O, Salmona M: Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. J Mol Biol. 2000 Jul 28;300(5):1309-22. [10903871 ]
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
Gene Name:
P2RY12
Uniprot ID:
Q9H244
Molecular Weight:
39438.355 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50368781
References
  1. Baqi Y, Atzler K, Kose M, Glanzel M, Muller CE: High-affinity, non-nucleotide-derived competitive antagonists of platelet P2Y12 receptors. J Med Chem. 2009 Jun 25;52(12):3784-93. doi: 10.1021/jm9003297. [19463000 ]
General Function:
Protein-arginine deiminase activity
Specific Function:
Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance. Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance. Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci. Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.
Gene Name:
PADI4
Uniprot ID:
Q9UM07
Molecular Weight:
74078.65 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50780 uMNot AvailableBindingDB 50368781
References
  1. Knuckley B, Luo Y, Thompson PR: Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. Bioorg Med Chem. 2008 Jan 15;16(2):739-45. Epub 2007 Oct 13. [17964793 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity).Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
Gene Name:
RORB
Uniprot ID:
Q92753
Molecular Weight:
53219.385 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.09 uMATG_RORb_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha 1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver, kidney and intestine.
Gene Name:
HNF4A
Uniprot ID:
P41235
Molecular Weight:
52784.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.30 uMATG_HNF4a_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Protein tyrosine/serine/threonine phosphatase activity
Specific Function:
Shows activity both for tyrosine-protein phosphate and serine-protein phosphate, but displays a strong preference toward phosphotyrosines. Specifically dephosphorylates and inactivates ERK1 and ERK2.
Gene Name:
DUSP3
Uniprot ID:
P51452
Molecular Weight:
20478.1 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.40 uMNVS_ENZ_hDUSP3Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.00 uMNot AvailableNot Available