Tmic
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Record Information
Version2.0
Creation Date2014-08-28 18:03:36 UTC
Update Date2014-12-24 20:26:34 UTC
Accession NumberT3D3950
Identification
Common NameDoxycycline
ClassSmall Molecule
DescriptionA synthetic tetracycline derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria (malaria, falciparum). [PubChem]
Compound Type
  • Anti-Bacterial Agent
  • Antimalarial
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Tetracycline
Chemical Structure
Thumb
Synonyms
Synonym
(4S,4AR,5S,5ar,6R,12as)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
5-Hydroxy-alpha-6-deoxytetracycline
6-alpha-deoxy-5-oxytetracycline
6alpha-Deoxy-5-oxytetracycline
6α-deoxy-5-oxytetracycline
Adoxa
Alodox
Atridox
Doryx
Doxcycline anhydrous
Doxiciclina
Doxy
Doxycin
Doxycyclin
Doxycycline (anhydrous)
Doxycycline Hyclate
Doxycycline Monohydrate
Doxycyclinum
Doxylin
Doxytetracycline
Jenacyclin
Microdox
Monodox
Morgidox
NicAzelDoxyKit
Nu-Doxycycline
Ocudox
Oracea
Periostat
Supracyclin
Vibra-Tabs
Vibramycin
Chemical FormulaC22H24N2O8
Average Molecular Mass444.435 g/mol
Monoisotopic Mass444.153 g/mol
CAS Registry Number564-25-0
IUPAC Name(4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
Traditional Namevibramycin
SMILES[H][C@]1(C)C2=C(C(O)=CC=C2)C(=O)C2=C(O)[C@]3(O)C(=O)C(C(O)=N)=C(O)[C@@]([H])(N(C)C)[C@]3([H])[C@@]([H])(O)[C@]12[H]
InChI IdentifierInChI=1S/C22H24N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31)/t7-,10+,14+,15-,17-,22-/m0/s1
InChI KeyInChIKey=JBIWCJUYHHGXTC-AKNGSSGZSA-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
  • Secondary alcohol
  • 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
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Bone Marrow
  • Heart
  • Liver
Pathways
NameSMPDB LinkKEGG Link
Doxycycline Action PathwaySMP00291 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point201°C
Boiling PointNot Available
Solubility630 mg/L (at 25°C)
LogP-0.02
Predicted Properties
PropertyValueSource
Water Solubility0.63 g/LALOGPS
logP-0.72ALOGPS
logP-3.4ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)-2.2ChemAxon
pKa (Strongest Basic)7.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area181.62 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity113.89 m³·mol⁻¹ChemAxon
Polarizability42.88 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, Positivesplash10-0zfr-5392300000-04bc3e193569d5361cd9View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-0002-1350309000-72de0c19abb90597f06eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004j-0000900000-026ab0fbae1dd1507067View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01t9-0101900000-b4323fa1f473089244d4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-2594400000-f2ce8a8f6861b3523262View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0111900000-972580ac62554c18b5b7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ue9-1347900000-0a4c864410c35dab696dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9274000000-977247efe53ffd07604dView in MoNA
Toxicity Profile
Route of ExposureCompletely absorbed following oral administration.
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. (4). 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.
MetabolismHepatic 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: 18-22 hours
Toxicity ValuesLD50=262 mg/kg (I.P. in rat).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesDoxycycline is indicated for use in respiratory tract infections caused by Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Legionella spp., or Klebsiella spp. It is also used for prophylaxis of malaria. Doxycycline is indicated for a variety of bacterial infections, from Mycobacterium fortuitum and M. marinum, to susceptible E. coli and Brucella spp. It can be used as an alternative to treating plague, tetanus, Campylobacter fetus
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.
SymptomsSymptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, 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.
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 IDDB00254
HMDB IDHMDB14399
PubChem Compound ID5281011
ChEMBL IDCHEMBL1433
ChemSpider ID4444486
KEGG IDC06973
UniProt IDNot Available
OMIM ID
ChEBI ID50845
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDDXT
ACToR IDNot Available
Wikipedia LinkDoxycycline
References
Synthesis Reference

Dai-Wu Seol, “DNA cassette for the production of secretable recombinant trimeric TRAIL proteins, tetracycline/ doxycycline-inducible adeno-associated virus vector, their combination and use in gene therapy.” U.S. Patent US20020128438, issued September 12, 2002.

MSDSLink
General References
  1. Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Buttner DW: Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol. 2003 Nov;192(4):211-6. Epub 2003 Mar 5. [12684759 ]
  2. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005 Jun 18-24;365(9477):2116-21. [15964448 ]
  3. Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ: Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2006 Sep;50(9):3124-31. [16940111 ]
  4. 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 ]
  5. Wikipedia. Doxycycline. Last Updated 23 August 2014. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Identical protein binding
Specific Function:
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Gene Name:
B2M
Uniprot ID:
P61769
Molecular Weight:
13714.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5047 uMNot AvailableBindingDB 92396
References
  1. Giorgetti S, Raimondi S, Pagano K, Relini A, Bucciantini M, Corazza A, Fogolari F, Codutti L, Salmona M, Mangione P, Colombo L, De Luigi A, Porcari R, Gliozzi A, Stefani M, Esposito G, Bellotti V, Stoppini M: Effect of tetracyclines on the dynamics of formation and destructuration of beta2-microglobulin amyloid fibrils. J Biol Chem. 2011 Jan 21;286(3):2121-31. doi: 10.1074/jbc.M110.178376. Epub 2010 Nov 10. [21068391 ]
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
Inhibitory630 uMNot AvailableBindingDB 92396
IC50860 uMNot AvailableBindingDB 92396
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 ]
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.00 uMNot AvailableNot Available