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Identification
NameColchicine
Accession NumberDB01394
TypeSmall Molecule
GroupsApproved
Description

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). [PubChem]

Structure
Thumb
Synonyms
Colchicin
Colchicina
Colchicinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Colchicinecapsule.6 mg/1oralWest ward Pharmaceutical Corp2014-10-01Not applicableUs
Colchicinetablet0.6 mgoralEuro Pharm International Canada Inc1974-12-31Not applicableCanada
Colchicinetablet, film coated.6 mg/1oralPrasco Laboratories2015-01-12Not applicableUs
Colchicinetablet1 mgoralEuro Pharm International Canada Inc1950-12-312012-06-14Canada
Colchicine Tab 0.6mgtablet0.6 mgoralAbbott Laboratories, Limited1951-12-312007-07-31Canada
Colchicine Tab 0.6mgtablet0.6 mgoralOdan Laboratories Ltd1982-12-31Not applicableCanada
Colchicine Tab 0.6mgtablet0.6 mgoralD.C. Labs Limited1969-12-312003-07-11Canada
Colchicine Tab 1mgtablet1 mgoralOdan Laboratories Ltd1985-12-312013-03-06Canada
Colcrystablet, film coated.6 mg/1oralCardinal Health2009-09-01Not applicableUs
Colcrystablet, film coated.6 mg/1oralPhysicians Total Care, Inc.2011-10-19Not applicableUs
Colcrystablet, film coated.6 mg/1oralAvera Mc Kennan Hospital2015-08-05Not applicableUs
Colcrystablet, film coated.6 mg/1oralREMEDYREPACK INC.2013-05-032016-04-05Us
Colcrystablet, film coated.6 mg/1oralREMEDYREPACK INC.2013-02-212016-04-05Us
Colcrystablet, film coated.6 mg/1oralTakeda Pharmaceuticals America, Inc.2009-09-01Not applicableUs
Colcrystablet, film coated.6 mg/1oralAphena Pharma Solutions Tennessee, Llc2009-09-01Not applicableUs
Colcrystablet, film coated.6 mg/1oralProficient Rx LP2009-09-01Not applicableUs
Colcrystablet, film coated.6 mg/1oralAR Scientific Inc.2009-09-01Not applicableUs
Jamp-colchicinetablet0.6 mgoralJamp Pharma Corporation2011-10-07Not applicableCanada
Jamp-colchicinetablet1.0 mgoralJamp Pharma Corporation2011-10-072013-04-03Canada
Mitigarecapsule.6 mg/1oralHikma Americas, Inc.2014-10-01Not applicableUs
PMS-colchicinetablet0.6 mgoralPharmascience Inc2013-02-27Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Probenecid and ColchicineWatson Laboratories, Inc.
Verban OntWelcker Lyster Ltd., Division Of Technilab Inc.
SaltsNot Available
Categories
UNIISML2Y3J35T
CAS number64-86-8
WeightAverage: 399.437
Monoisotopic: 399.168187537
Chemical FormulaC22H25NO6
InChI KeyInChIKey=IAKHMKGGTNLKSZ-UHFFFAOYSA-N
InChI
InChI=1S/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)
IUPAC Name
N-{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
SMILES
COC1=CC2=C(C(OC)=C1OC)C1=CC=C(OC)C(=O)C=C1C(CC2)NC(C)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as tropones. These 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
  • Tropone
  • Anisole
  • Alkyl aryl ether
  • Benzenoid
  • Acetamide
  • Cyclic ketone
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Ether
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationFor treatment and relief of pain in attacks of acute gouty arthritis.
PharmacodynamicsColchicine is a highly poisonous alkaloid, originally extracted from plants of the genus Colchicum (Autumn crocus, also known as the "Meadow saffron"). Originally used to treat rheumatic complaints and especially gout, it was also prescribed for its cathartic and emetic effects. Its present medicinal use is mainly in the treatment of gout; as well, it is being investigated for its potential use as an anti-cancer drug. It can also be used as initial treatment for pericarditis and preventing recurrences of the condition.
Mechanism of actionThe 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.
Related Articles
AbsorptionColchicine 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.
Volume of distribution
  • 5 to 8 L/kg [healthy young volunteers]
Protein bindingLow to moderate (30 to 50%).
Metabolism

Probably hepatic. Although colchicine metabolites have not been identified in humans, metabolism by mammalian hepatic microsomes has been demonstrated in vitro.

Route of eliminationIn 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 lifeElimination 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.
Clearance
  • 0.17 L/hr/kg [familial Mediterranean fever patients with end-stage renal disease]
  • 0.73 L/hr/kg [familial Mediterranean fever patients with normal renal function]
ToxicityThe onset of toxic effects is usually delayed for several hours or more after the ingestion of an acute overdose. Nausea, vomiting, abdominal pain, and diarrhea occur first. The diarrhea may be bloody due to hemorrhagic gastroenteritis. Burning sensations of the throat, stomach, and skin may be prominent symptoms. Extensive vascular damage may result in shock. Kidney damage, evidenced by hematuria and oliguria, may occur. Muscular weakness may be marked, and ascending paralysis of the central nervous system may develop; the patient usually remains conscious. Delirium and convulsions may occur. Death due to respiratory arrest may result. Although death from the ingestion of as little as 7 mg has been reported, much larger doses have been survived .
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9856
Blood Brain Barrier+0.7865
Caco-2 permeable+0.5119
P-glycoprotein substrateNon-substrate0.594
P-glycoprotein inhibitor INon-inhibitor0.8007
P-glycoprotein inhibitor IINon-inhibitor0.6956
Renal organic cation transporterNon-inhibitor0.8997
CYP450 2C9 substrateNon-substrate0.8042
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7359
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7959
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9208
BiodegradationReady biodegradable0.6489
Rat acute toxicity2.3748 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9877
hERG inhibition (predictor II)Non-inhibitor0.7394
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral.6 mg/1
Tabletoral0.6 mg
Tabletoral1 mg
Tablet, film coatedoral.6 mg/1
Tabletoral1.0 mg
Tabletoral
Ointmenttopical
Prices
Unit descriptionCostUnit
Colchicine powder306.6USD g
Colcrys 0.6 mg tablet5.82USD tablet
Colchicine 0.6 mg tablet0.58USD tablet
Colchicine 1 mg Tablet0.55USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7601758 No2009-02-102029-02-10Us
US7619004 No2008-12-032028-12-03Us
US7820681 No2009-02-172029-02-17Us
US7906519 No2009-02-172029-02-17Us
US7915269 No2009-02-172029-02-17Us
US7935731 No2008-12-032028-12-03Us
US7964647 No2008-10-062028-10-06Us
US7964648 No2008-10-062028-10-06Us
US7981938 No2008-10-062028-10-06Us
US8093296 No2008-10-062028-10-06Us
US8093297 No2008-10-062028-10-06Us
US8093298 No2008-10-062028-10-06Us
US8097655 No2008-10-062028-10-06Us
US8415395 No2008-10-062028-10-06Us
US8415396 No2008-10-062028-10-06Us
US8440721 No2009-02-172029-02-17Us
US8440722 No2009-02-172029-02-17Us
US8927607 No2013-08-222033-08-22Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156 °CPhysProp
water solubility4.5E+004 mg/L (at 25 °C)SEIDELL,A (1941)
logP1.30HANSCH,C ET AL. (1995)
pKa1.85SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0276 mg/mLALOGPS
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 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity111.38 m3·mol-1ChemAxon
Polarizability42.41 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (2.96 KB)
SpectraNot Available
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.

US20040138182
General ReferencesNot Available
External Links
ATC CodesM04AC01
AHFS Codes
  • 92:00.00
  • 92:02.00*
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (74.9 KB)
Interactions
Drug Interactions
Drug
AbirateroneThe serum concentration of Colchicine can be increased when it is combined with Abiraterone.
AmiodaroneThe serum concentration of Colchicine can be increased when it is combined with Amiodarone.
AprepitantThe serum concentration of Colchicine can be increased when it is combined with Aprepitant.
AtazanavirThe serum concentration of Colchicine can be increased when it is combined with Atazanavir.
AtorvastatinColchicine may increase the myopathic rhabdomyolysis activities of Atorvastatin.
AzithromycinThe serum concentration of Colchicine can be increased when it is combined with Azithromycin.
BezafibrateBezafibrate may increase the myopathic rhabdomyolysis activities of Colchicine.
BoceprevirThe serum concentration of Colchicine can be increased when it is combined with Boceprevir.
CarvedilolThe serum concentration of Colchicine can be increased when it is combined with Carvedilol.
CeritinibThe serum concentration of Colchicine can be increased when it is combined with Ceritinib.
Choline C 11The therapeutic efficacy of Choline C 11 can be decreased when used in combination with Colchicine.
ClarithromycinThe serum concentration of Colchicine can be increased when it is combined with Clarithromycin.
CobicistatThe serum concentration of Colchicine can be increased when it is combined with Cobicistat.
ConivaptanThe serum concentration of Colchicine can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Colchicine can be increased when it is combined with Crizotinib.
CyanocobalaminThe serum concentration of Cyanocobalamin can be decreased when it is combined with Colchicine.
CyclosporineThe serum concentration of Colchicine can be increased when it is combined with Cyclosporine.
DaclatasvirThe serum concentration of Colchicine can be increased when it is combined with Daclatasvir.
DarunavirThe serum concentration of Colchicine can be increased when it is combined with Darunavir.
DasatinibThe serum concentration of Colchicine can be increased when it is combined with Dasatinib.
DelavirdineThe serum concentration of Colchicine can be increased when it is combined with Delavirdine.
DigoxinThe serum concentration of Colchicine can be increased when it is combined with Digoxin.
DiltiazemThe serum concentration of Colchicine can be increased when it is combined with Diltiazem.
DipyridamoleThe serum concentration of Colchicine can be increased when it is combined with Dipyridamole.
DronedaroneThe serum concentration of Colchicine can be increased when it is combined with Dronedarone.
EliglustatThe serum concentration of Colchicine can be increased when it is combined with Eliglustat.
ErythromycinThe serum concentration of Colchicine can be increased when it is combined with Erythromycin.
FenofibrateFenofibrate may increase the myopathic rhabdomyolysis activities of Colchicine.
FlibanserinThe serum concentration of Colchicine can be increased when it is combined with Flibanserin.
FluconazoleThe serum concentration of Colchicine can be increased when it is combined with Fluconazole.
FluvastatinColchicine may increase the myopathic rhabdomyolysis activities of Fluvastatin.
FosamprenavirThe serum concentration of Colchicine can be increased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Colchicine can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Colchicine can be increased when it is combined with Fusidic Acid.
GemfibrozilGemfibrozil may increase the myopathic rhabdomyolysis activities of Colchicine.
IbrutinibThe serum concentration of Colchicine can be increased when it is combined with Ibrutinib.
IdelalisibThe serum concentration of Colchicine can be increased when it is combined with Idelalisib.
ImatinibThe serum concentration of Colchicine can be increased when it is combined with Imatinib.
IndinavirThe serum concentration of Colchicine can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Colchicine can be increased when it is combined with Isavuconazonium.
ItraconazoleThe serum concentration of Colchicine can be increased when it is combined with Itraconazole.
IvacaftorThe serum concentration of Colchicine can be increased when it is combined with Ivacaftor.
KetoconazoleThe serum concentration of Colchicine can be increased when it is combined with Ketoconazole.
LapatinibThe serum concentration of Colchicine can be increased when it is combined with Lapatinib.
LomitapideThe serum concentration of Colchicine can be increased when it is combined with Lomitapide.
LovastatinColchicine may increase the myopathic rhabdomyolysis activities of Lovastatin.
LuliconazoleThe serum concentration of Colchicine can be increased when it is combined with Luliconazole.
LumacaftorThe serum concentration of Colchicine can be decreased when it is combined with Lumacaftor.
MefloquineThe serum concentration of Colchicine can be increased when it is combined with Mefloquine.
MifepristoneThe serum concentration of Colchicine can be increased when it is combined with Mifepristone.
MirabegronThe serum concentration of Colchicine can be increased when it is combined with Mirabegron.
NefazodoneThe serum concentration of Colchicine can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Colchicine can be increased when it is combined with Nelfinavir.
NicardipineThe serum concentration of Colchicine can be increased when it is combined with Nicardipine.
NilotinibThe serum concentration of Colchicine can be increased when it is combined with Nilotinib.
PalbociclibThe serum concentration of Colchicine can be increased when it is combined with Palbociclib.
PitavastatinColchicine may increase the myopathic rhabdomyolysis activities of Pitavastatin.
PosaconazoleThe serum concentration of Colchicine can be increased when it is combined with Posaconazole.
PravastatinColchicine may increase the myopathic rhabdomyolysis activities of Pravastatin.
ProgesteroneThe serum concentration of Colchicine can be increased when it is combined with Progesterone.
PropranololThe serum concentration of Colchicine can be increased when it is combined with Propranolol.
QuinidineThe serum concentration of Colchicine can be increased when it is combined with Quinidine.
QuinineThe serum concentration of Colchicine can be increased when it is combined with Quinine.
RanolazineThe serum concentration of Colchicine can be increased when it is combined with Ranolazine.
ReserpineThe serum concentration of Colchicine can be increased when it is combined with Reserpine.
RitonavirThe serum concentration of Colchicine can be increased when it is combined with Ritonavir.
RolapitantThe serum concentration of Colchicine can be increased when it is combined with Rolapitant.
RosuvastatinColchicine may increase the myopathic rhabdomyolysis activities of Rosuvastatin.
SaquinavirThe serum concentration of Colchicine can be increased when it is combined with Saquinavir.
SimeprevirThe serum concentration of Colchicine can be increased when it is combined with Simeprevir.
SimvastatinColchicine may increase the myopathic rhabdomyolysis activities of Simvastatin.
StiripentolThe serum concentration of Colchicine can be increased when it is combined with Stiripentol.
SunitinibThe serum concentration of Colchicine can be increased when it is combined with Sunitinib.
TacrolimusThe serum concentration of Colchicine can be increased when it is combined with Tacrolimus.
TamoxifenThe serum concentration of Colchicine can be increased when it is combined with Tamoxifen.
TelaprevirThe serum concentration of Colchicine can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Colchicine can be increased when it is combined with Telithromycin.
TesmilifeneThe serum concentration of Colchicine can be decreased when it is combined with Tesmilifene.
TipranavirThe serum concentration of Colchicine can be increased when it is combined with Tipranavir.
VandetanibThe serum concentration of Colchicine can be increased when it is combined with Vandetanib.
VemurafenibThe serum concentration of Colchicine can be increased when it is combined with Vemurafenib.
VerapamilThe serum concentration of Colchicine can be increased when it is combined with Verapamil.
VoriconazoleThe serum concentration of Colchicine can be increased when it is combined with Voriconazole.
Food Interactions
  • Avoid alcohol since it increases uric acid levels.
  • Drink liberally.
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15720245 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:15720245 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitorinducer
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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase.
Gene Name:
CYP2B6
Uniprot ID:
P20813
Molecular Weight:
56277.81 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitorinducer
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular Weight:
55824.275 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitorinducer
General Function:
Steroid 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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent phospholipid efflux translocator that acts as a positive regulator of biliary lipid secretion. Functions as a floppase that translocates specifically phosphatidylcholine (PC) from the inner to the outer leaflet of the canalicular membrane bilayer into the canaliculi of hepatocytes. Translocation of PC makes the biliary phospholipids available for extraction into the canaliculi ...
Gene Name:
ABCB4
Uniprot ID:
P21439
Molecular Weight:
141521.845 Da
References
  1. Vollrath V, Wielandt AM, Acuna C, Duarte I, Andrade L, Chianale J: Effect of colchicine and heat shock on multidrug resistance gene and P-glycoprotein expression in rat liver. J Hepatol. 1994 Nov;21(5):754-63. [PubMed:7890890 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
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
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. [PubMed:10196521 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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
References
  1. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, Serabjit-Singh CS: Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther. 2001 Nov;299(2):620-8. [PubMed:11602674 ]
  2. 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. [PubMed:12699389 ]
  3. Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103 ]
  4. Troutman MD, Thakker DR: Novel experimental parameters to quantify the modulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Pharm Res. 2003 Aug;20(8):1210-24. [PubMed:12948019 ]
  5. Ambudkar SV, Lelong IH, Zhang J, Cardarelli CO, Gottesman MM, Pastan I: Partial purification and reconstitution of the human multidrug-resistance pump: characterization of the drug-stimulatable ATP hydrolysis. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8472-6. [PubMed:1356264 ]
  6. Bebawy M, Morris MB, Roufogalis BD: A continuous fluorescence assay for the study of P-glycoprotein-mediated drug efflux using inside-out membrane vesicles. Anal Biochem. 1999 Mar 15;268(2):270-7. [PubMed:10075817 ]
  7. Kuo CC, Hsieh HP, Pan WY, Chen CP, Liou JP, Lee SJ, Chang YL, Chen LT, Chen CT, Chang JY: BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004 Jul 1;64(13):4621-8. [PubMed:15231674 ]
  8. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR Jr, Chen X, Chen ZS: Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol. 2009 Jul 15;78(2):153-61. doi: 10.1016/j.bcp.2009.04.002. Epub 2009 Apr 11. [PubMed:19427995 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.
Gene Name:
ABCC1
Uniprot ID:
P33527
Molecular Weight:
171589.5 Da
References
  1. Stride BD, Grant CE, Loe DW, Hipfner DR, Cole SP, Deeley RG: Pharmacological characterization of the murine and human orthologs of multidrug-resistance protein in transfected human embryonic kidney cells. Mol Pharmacol. 1997 Sep;52(3):344-53. [PubMed:9281595 ]
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Drug created on July 08, 2007 11:02 / Updated on July 29, 2016 01:53