Colchicine (T3D4020)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (10)XML
Targets (10)
Record Information
Version2.0
Creation Date2014-08-29 04:49:18 UTC
Update Date2014-12-24 20:26:35 UTC
Accession NumberT3D4020
Identification
Common NameColchicine
ClassSmall Molecule
DescriptionColchicine is only found in individuals that have used or taken this drug. It is a major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (periodic disease). The precise mechanism of action has not been completely established. In patients with gout, colchicine apparently interrupts the cycle of monosodium urate crystal deposition in joint tissues and the resultant inflammatory response that initiates and sustains an acute attack. Colchicine decreases leukocyte chemotaxis and phagocytosis and inhibits the formation and release of a chemotactic glycoprotein that is produced during phagocytosis of urate crystals. Colchicine also inhibits urate crystal deposition, which is enhanced by a low pH in the tissues, probably by inhibiting oxidation of glucose and subsequent lactic acid production in leukocytes. Colchicine has no analgesic or antihyperuricemic activity. Colchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved.
Compound Type
  • Drug
  • Ester
  • Ether
  • Gout Suppressant
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Plant Toxin
  • Tubulin Modulator
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
Colchicin
Colchicina
Colchicinum
Colcrys
Chemical FormulaC22H25NO6
Average Molecular Mass399.437 g/mol
Monoisotopic Mass399.168 g/mol
CAS Registry Number64-86-8
IUPAC NameN-{3,4,5,14-tetramethoxy-13-oxotricyclo[9.5.0.0²,⁷]hexadeca-1(16),2(7),3,5,11,14-hexaen-10-yl}acetamide
Traditional Namecolchicine
SMILESCOC1=C(OC)C(OC)=C2C(CCC(N=C(C)O)C3=CC(=O)C(OC)=CC=C23)=C1
InChI IdentifierInChI=1/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)
InChI KeyInChIKey=IAKHMKGGTNLKSZ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tropones. Tropones are compounds containing a tropone ring, which is a cycloheptatrienone ring bearing a ketone group.
KingdomOrganic compounds
Super ClassHydrocarbon derivatives
ClassTropones
Sub ClassNot Available
Direct ParentTropones
Alternative Parents
Substituents
  • Anisole
  • Tropone
  • Alkyl aryl ether
  • Benzenoid
  • Cyclic ketone
  • Carboximidic acid
  • Carboximidic acid derivative
  • Ether
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point156°C
Boiling PointNot Available
Solubility4.5E+004 mg/L (at 25°C)
LogP1.3
Predicted Properties
PropertyValueSource
Water Solubility0.028 g/LALOGPS
logP1.59ALOGPS
logP1.46ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)15.06ChemAxon
pKa (Strongest Basic)-0.038ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.09 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity111.38 m³·mol⁻¹ChemAxon
Polarizability42.41 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-053u-1009000000-7a8d292bb6a5673c9d7c2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0000900000-c73c5a28a750cece607a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0049400000-2a76bd81d41e1bc5925c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0gba-0091000000-fb24bc910ffe7bd748112017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-03gi-0096000000-1604b0f123208b25b9492021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0zfr-0029400000-dc08a845d6fb327eec562021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0000900000-d360bbc1ca27b2e657d42021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0000900000-44e9ac8566ca5c6846032021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0000900000-9d973f7afeacb8db799d2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-0gc1-0192000000-dcb2736f710df3f17b012021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0udi-0049500000-27383218cdc6487393072021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0gba-0091000000-fb24bc910ffe7bd748112021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0zfr-0009700000-00c1abf086f6716cac6b2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0009100000-4f6b3c625a68879816702016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05dl-0049000000-75fafbc5e28d11766c0c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0009000000-cc76299babee13af85022016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0537-1009000000-247faa52698339d3e5442016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pi3-9077000000-eb1350fc19fa611668aa2016-08-04View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0001900000-958a463c4e2f7c3dd5882021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udl-0009500000-8181c90153beb9e9a4f52021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052g-5079000000-81182c306cc4f86cf2c32021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0009000000-b40b49dac61f8e9864fa2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-7009000000-666c5fffe6918e3020f72021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9007000000-7e1ec907f14345d7e9922021-10-11View Spectrum
Toxicity Profile
Route of ExposureColchicine is rapidly absorbed after oral administration, probably from the jejunum and ileum. However, the rate and extent of absorption are variable, depending on the tablet dissolution rate; variability in gastric emptying, intestinal motility, and pH at the absorption site; and the extent to which colchicine is bound to microtubules in gastrointestinal mucosal cells.
Mechanism of ToxicityColchicine inhibits microtubule assembly in various cells, including leukocytes, probably by binding to and interfering with polymerization of the microtubule subunit tubulin. Although some studies have found that this action probably does not contribute significantly to colchicine's antigout action, a recent in vitro study has shown that it may be at least partially involved.
MetabolismProbably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro. Route of Elimination: In healthy volunteers (n=12) 40 - 65% of 1 mg orally administered colchicine was recovered unchanged in urine. Enterohepatic recirculation and biliary excretion are also postulated to play a role in colchicine elimination. Half Life: Elimination half-life is approximately 1 hour in healthy subjects, although a study with an extended sampling time reported mean terminal elimination half-life values of approximately 9 to 10.5 hours. Other studies have reported half-life values of approximately 2 hours in patients with alcoholic cirrhosis and approximately 2.5 hours in patients with familial Mediterranean fever.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor treatment and relief of pain in attacks of acute gouty arthritis.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01394
HMDB IDHMDB15466
PubChem Compound ID2833
ChEMBL IDCHEMBL107
ChemSpider ID2731
KEGG IDC07592
UniProt IDNot Available
OMIM ID
ChEBI ID23359
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkColchicine
References
Synthesis Reference

Christian Wehrey, “Colchicine derivatives, process for preparing them, products obtained therefrom and use thereof.” U.S. Patent US20040138182, issued July 15, 2004.

MSDSLink
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Tubulin beta-1 chain
General Function:
Structural constituent of cytoskeleton
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
Gene Name:
TUBB1
Uniprot ID:
Q9H4B7
Molecular Weight:
50326.56 Da
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. [17139284 ]
  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. [17016423 ]
  3. Acharya BR, Choudhury D, Das A, Chakrabarti G: Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74. doi: 10.1021/bi900152k. [19527023 ]
  4. Li CM, Lu Y, Ahn S, Narayanan R, Miller DD, Dalton JT: Competitive mass spectrometry binding assay for characterization of three binding sites of tubulin. J Mass Spectrom. 2010 Oct;45(10):1160-6. doi: 10.1002/jms.1804. [20814887 ]
  5. Finkelstein Y, Aks SE, Hutson JR, Juurlink DN, Nguyen P, Dubnov-Raz G, Pollak U, Koren G, Bentur Y: Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila). 2010 Jun;48(5):407-14. doi: 10.3109/15563650.2010.495348. [20586571 ]
  6. Cerquaglia C, Diaco M, Nucera G, La Regina M, Montalto M, Manna R: Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):117-24. [15720245 ]
Target Details
2. Tubulin beta chain
General Function:
Ubiquitin protein ligase binding
Specific Function:
Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain.
Gene Name:
TUBB
Uniprot ID:
P07437
Molecular Weight:
49670.515 Da
References
  1. Yee KW, Hagey A, Verstovsek S, Cortes J, Garcia-Manero G, O'Brien SM, Faderl S, Thomas D, Wierda W, Kornblau S, Ferrajoli A, Albitar M, McKeegan E, Grimm DR, Mueller T, Holley-Shanks RR, Sahelijo L, Gordon GB, Kantarjian HM, Giles FJ: Phase 1 study of ABT-751, a novel microtubule inhibitor, in patients with refractory hematologic malignancies. Clin Cancer Res. 2005 Sep 15;11(18):6615-24. [16166440 ]
  2. Acharya BR, Choudhury D, Das A, Chakrabarti G: Vitamin K3 disrupts the microtubule networks by binding to tubulin: a novel mechanism of its antiproliferative activity. Biochemistry. 2009 Jul 28;48(29):6963-74. doi: 10.1021/bi900152k. [19527023 ]
  3. Li CM, Lu Y, Ahn S, Narayanan R, Miller DD, Dalton JT: Competitive mass spectrometry binding assay for characterization of three binding sites of tubulin. J Mass Spectrom. 2010 Oct;45(10):1160-6. doi: 10.1002/jms.1804. [20814887 ]
  4. Cerquaglia C, Diaco M, Nucera G, La Regina M, Montalto M, Manna R: Pharmacological and clinical basis of treatment of Familial Mediterranean Fever (FMF) with colchicine or analogues: an update. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):117-24. [15720245 ]
Target Details
3. Cytochrome P450 3A4
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50014846
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
Target Details
4. Multidrug resistance protein 1
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>50 uMNot AvailableBindingDB 50014846
References
  1. Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J: Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. [12699389 ]
Target Details
5. Nuclear receptor subfamily 0 group B member 1
General Function:
Transcription factor binding
Specific Function:
Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency (By similarity).
Gene Name:
NR0B1
Uniprot ID:
P51843
Molecular Weight:
51717.185 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>67.57 uMNot AvailableBindingDB 50014846
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
6. Solute carrier family 22 member 3
General Function:
Toxin transporter activity
Specific Function:
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name:
SLC22A3
Uniprot ID:
O75751
Molecular Weight:
61279.485 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.12 uMNot AvailableBindingDB 50014846
References
  1. Grundemann D, Schechinger B, Rappold GA, Schomig E: Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci. 1998 Sep;1(5):349-51. [10196521 ]
Target Details
7. Steroidogenic factor 1
General Function:
Zinc ion binding
Specific Function:
Transcriptional activator. Seems to be essential for sexual differentiation and formation of the primary steroidogenic tissues. Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional avtivity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.
Gene Name:
NR5A1
Uniprot ID:
Q13285
Molecular Weight:
51635.47 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>67.57 uMNot AvailableBindingDB 50014846
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
8. ATPase family AAA domain-containing protein 5
General Function:
Atp binding
Specific Function:
Involved in DNA damage response. Involved in a RAD9A-related damage checkpoint, a pathway that is important in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis. Modulates the RAD9A interaction with BCL2 and thereby induces DNA damages-induced apoptosis.
Gene Name:
ATAD5
Uniprot ID:
Q96QE3
Molecular Weight:
207568.185 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.06 uMTox21_ELG1_LUC_AgonistTox21/NCGC
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 ]
Target Details
9. Proto-oncogene c-Fos
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. In the heterodimer, FOS and JUN/AP-1 basic regions each seems to interact with symmetrical DNA half sites. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum.
Gene Name:
FOS
Uniprot ID:
P01100
Molecular Weight:
40694.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.15 uMATG_AP_1_CISAttagene
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 ]
Target Details
10. Cellular tumor antigen p53
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
TP53
Uniprot ID:
P04637
Molecular Weight:
43652.79 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.61 uMAPR_p53Act_24h_upApredica
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 ]