Identification

Name
Colchicine
Accession Number
DB01394
Type
Small Molecule
Groups
Approved
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
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ColchicineCapsule0.6 mg/1Oralbryant ranch prepack2014-10-01Not applicableUs
ColchicineCapsule0.6 mg/1OralAmerincan Health Packaging2018-04-01Not applicableUs
ColchicineTablet1 mgOralEuro Pharm International Canada Inc1950-12-312012-06-14Canada
ColchicineCapsule0.6 mg/1OralA-S Medication Solutions2014-10-01Not applicableUs
ColchicineCapsule0.6 mg/1OralWest-Ward Pharmaceuticals Corp2014-10-01Not applicableUs0143 301820180913 8702 ndobl1
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 0.6mgTablet0.6 mgOralAbbott1951-12-312007-07-31Canada
Colchicine Tab 1mgTablet1 mgOralOdan Laboratories Ltd1985-12-312013-03-06Canada
ColcrysTablet, film coated0.6 mg/1OralRemedy Repack2013-05-032013-05-04Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ColchicineTablet, film coated0.6 mg/1OralPrasco Laboratories2015-01-122021-10-31Us66993 0165 02 nlmimage10 8e404752
ColchicineTablet, film coated0.6 mg/1OralAmerincan Health Packaging2017-07-132018-12-31Us
ColchicineTablet, film coated0.6 mg/1OralAmerican Health Packaging2018-08-01Not applicableUs
ColchicineTablet0.6 mg/1OralAmneal Pharmaceuticals of New York Llc2016-09-30Not applicableUs
ColchicineTablet, film coated0.6 mg/1OralPar Pharmaceutical2018-07-01Not applicableUs
Euro-colchicineTablet0.6 mgOralEuro Pharm International Canada IncNot applicableNot applicableCanada
Jamp-colchicineTablet0.6 mgOralJamp Pharma Corporation2011-10-07Not applicableCanada
Jamp-colchicineTablet1.0 mgOralJamp Pharma Corporation2011-10-072013-04-03Canada
PMS-colchicineTablet0.6 mgOralPharmascience Inc2013-02-27Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Probenecid and ColchicineColchicine (0.5 mg/1) + Probenecid (500 mg/1)TabletOralIngenus Pharmaceuticals Nj, Llc2008-05-132008-05-13Us
Probenecid and ColchicineColchicine (0.5 mg/1) + Probenecid (500 mg/1)TabletOralRising Pharmaceuticals2008-05-13Not applicableUs
Probenecid and ColchicineColchicine (0.5 mg/1) + Probenecid (500 mg/1)TabletOralAv Kare, Inc.2012-05-082016-02-01Us
Probenecid and ColchicineColchicine (0.5 mg/1) + Probenecid (500 mg/1)TabletOralActavis Pharma Company1982-10-01Not applicableUs00591 5325 01 nlmimage10 240e1210
Probenecid and ColchicineColchicine (0.5 mg/1) + Probenecid (500 mg/1)TabletOralPhysicians Total Care, Inc.1995-04-242013-05-30Us
Verban OntColchicine (100 mg) + Podophyllin (2 g)OintmentTopicalWelcker Lyster Ltd., Division Of Technilab Inc.1963-12-311999-09-17Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
ColchicineColchicine (0.6 mg/1)TabletOralRemedy Repack2010-11-102011-11-10Us
ColchicineColchicine (0.6 mg/1)TabletOralWest Ward Pharmaceutical1990-10-082010-12-28Us0143 120120180906 25352 1nfrw6k
ColchicineColchicine (0.6 mg/1)TabletOralRebel Distributors1990-10-082011-04-13Us
ColchicineColchicine (0.6 mg/1)TabletOralPhysicians Total Care, Inc.1995-05-122010-12-29Us
Categories
UNII
SML2Y3J35T
CAS number
64-86-8
Weight
Average: 399.437
Monoisotopic: 399.168187537
Chemical Formula
C22H25NO6
InChI Key
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

Pharmacology

Indication

For treatment and relief of pain in attacks of acute gouty arthritis.

Associated Conditions
Pharmacodynamics

Colchicine 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 action

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.

TargetActionsOrganism
ATubulin beta-1 chain
inhibitor
Human
ATubulin beta chain
inhibitor
Human
Absorption

Colchicine 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 binding

Low 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 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.

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]
Toxicity

The 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbemaciclibThe serum concentration of Colchicine can be increased when it is combined with Abemaciclib.
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Colchicine.
AcetaminophenThe serum concentration of Colchicine can be increased when it is combined with Acetaminophen.
Acetyl sulfisoxazoleThe serum concentration of Colchicine can be increased when it is combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Colchicine.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Colchicine.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Colchicine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Colchicine.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Colchicine which could result in a higher serum level.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Colchicine.
Food Interactions
  • Avoid alcohol since it increases uric acid levels.
  • Drink liberally.
  • Take without regard to meals.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0015466
KEGG Drug
D00570
KEGG Compound
C07592
PubChem Compound
2833
PubChem Substance
46505639
ChemSpider
2731
ChEBI
23359
ChEMBL
CHEMBL87
Therapeutic Targets Database
DAP001254
PharmGKB
PA449092
IUPHAR
2367
Guide to Pharmacology
GtP Drug Page
HET
LOC
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Colchicine
ATC Codes
M04AC01 — Colchicine
AHFS Codes
  • 92:16.00 — Antigout Agents
MSDS
Download (74.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceAcute Gouty Arthritis / Hypertriglyceridemias / Pericarditis1
1CompletedBasic ScienceFamilial Mediterranean Fever (FMF )1
1CompletedBasic ScienceHealthy Volunteers6
1CompletedBasic ScienceHealthy Volunteers / Pharmacokinetics1
1CompletedBasic ScienceHealthy; Adult; Volunteer; Colchicine; Pharmacokinetics; Diltiazem; Cytochrome p450 3A4; P-glycoprotein1
1CompletedBasic SciencePharmacokinetics11
1CompletedTreatmentRenal Replacement Therapies1
1RecruitingTreatmentAcute Gouty Arthritis1
1Unknown StatusTreatmentLiver Cirrhosis1
1, 2CompletedTreatmentBMI >30 kg/m2 / Metabolic Diseases1
1, 2RecruitingTreatmentDiabetic Nephropathies1
2CompletedPreventionAcute Gouty Arthritis1
2CompletedSupportive CareAtherosclerotic Vascular Diseases1
2CompletedTreatmentAcute Gouty Arthritis3
2CompletedTreatmentAcute Gouty Arthritis / Hyperuricemia3
2CompletedTreatmentAcute Gouty Arthritis / Moderate Renal Impairment1
2CompletedTreatmentBehcet's Syndrome1
2RecruitingOtherCoronary Artery Disease1
2RecruitingOtherCoronary Artery Disease / Human Immunodeficiency Virus (HIV)1
2RecruitingTreatmentColchicine / Coronary Artery Disease / Diarrhea / Inflammatory Reaction / Type 2 Diabetes Mellitus / White Blood Cell1
2RecruitingTreatmentCutaneous Polyarteritis Nodosa / Henoch-Schönlein Purpura / IgA Vasculitis / Primary Cutaneous Vasculitis1
2RecruitingTreatmentHepatocellular,Carcinoma / Invasion / Metastasis1
2RecruitingTreatmentMyocardial Infarction1
2RecruitingTreatmentNonvalvular Atrial Fibrillation1
2TerminatedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2Unknown StatusTreatmentDiabetic Nephropathies1
2Unknown StatusTreatmentStomatitis, Aphthous1
2WithdrawnTreatmentProstate Cancer1
2, 3CompletedTreatmentAcute Coronary Syndromes (ACS)1
2, 3CompletedTreatmentKnee Osteoarthritis (Knee OA)1
2, 3RecruitingTreatmentHeart Diseases / Single-ventricle1
3CompletedPreventionArrythmias1
3CompletedPreventionNonvalvular Atrial Fibrillation / Thoracic Surgery1
3CompletedPreventionPostpericardiotomy Syndrome1
3CompletedTreatmentAcute Gouty Arthritis2
3CompletedTreatmentLiver Cirrhosis, Biliary1
3CompletedTreatmentPericarditis1
3CompletedTreatmentPericarditis / Recurrences1
3Not Yet RecruitingPreventionAtrial Flutter / Nonvalvular Atrial Fibrillation / Thoracic Surgery1
3Not Yet RecruitingPreventionStrokes / Transient Ischaemic Attack (TIA)1
3RecruitingPreventionColchicine Adverse Reaction / Nonvalvular Atrial Fibrillation / Surgery, Cardiac1
3RecruitingPreventionCoronary Artery Disease / Myocardial Infarction1
3RecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
3RecruitingTreatmentChondrocalcinosis pyrophosphate1
3RecruitingTreatmentST Elevation Myocardial Infarction1
3Unknown StatusPreventionNonvalvular Atrial Fibrillation / Pericardial Effusion / Pleural Effusions / Post-pericardiotomy Syndrome / Surgery, Cardiac1
3Unknown StatusTreatmentConstriction / Nonvalvular Atrial Fibrillation / Post-pericardiotomy Syndrome1
3Unknown StatusTreatmentRhegmatogenous Retinal Detachments1
3WithdrawnTreatmentAsthma Bronchial / Chronic Lung Diseases1
4Active Not RecruitingTreatmentAcute Gouty Arthritis1
4CompletedBasic ScienceChronic Kidney Disease (CKD)1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedBasic SciencePharmacokinetics1
4CompletedDiagnosticAcute Gouty Arthritis1
4CompletedTreatmentAcute Gouty Arthritis1
4CompletedTreatmentElective Coronary Artery Bypass Graft Surgery1
4CompletedTreatmentFamilial Mediterranean Fever (FMF )1
4CompletedTreatmentHealthy Volunteers1
4CompletedTreatmentIntercritical Gout1
4CompletedTreatmentPericarditis / Recurrences1
4CompletedTreatmentPrimary Gout1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / Coronary Artery Disease1
4RecruitingTreatmentAcute Myocardial Infarction (AMI)1
4RecruitingTreatmentCoronary Artery Disease1
4RecruitingTreatmentManipulation Under Anesthesia1
4RecruitingTreatmentMyocardial Infarction1
4RecruitingTreatmentPericardial Effusion1
4Unknown StatusTreatmentAcute Coronary Syndromes (ACS)1
4Unknown StatusTreatmentAcute Myocardial Infarction (AMI)1
Not AvailableActive Not RecruitingTreatmentDiabetic Nephropathies1
Not AvailableCompletedTreatmentFibrosis, Liver1
Not AvailableUnknown StatusTreatmentCalcific Tendonitis1
Not AvailableWithdrawnTreatmentNon ST Segment Elevation Myocardial Infarction (NSTEMI)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amneal Pharmaceuticals
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Bedford Labs
  • Bryant Ranch Prepack
  • Comprehensive Consultant Services Inc.
  • Concord Labs
  • Consolidated Midland Corp.
  • DispenseXpress Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Excellium Pharmaceutical Inc.
  • Heartland Repack Services LLC
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Redpharm Drug
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Schein Pharmaceutical Inc.
  • Southwood Pharmaceuticals
  • Spectrum Pharmaceuticals
  • Sunrise Pharmaceutical Inc.
  • United Research Laboratories Inc.
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • Vision Pharma LLC
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
CapsuleOral0.6 mg/1
TabletOral0.6 mg/1
TabletOral1 mg
TabletOral0.6 mg
Tablet, film coatedOral0.6 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)
US7601758No2009-02-102029-02-10Us
US7619004No2008-12-032028-12-03Us
US7820681No2009-02-172029-02-17Us
US7906519No2009-02-172029-02-17Us
US7915269No2009-02-172029-02-17Us
US7935731No2008-12-032028-12-03Us
US7964647No2008-10-062028-10-06Us
US7964648No2008-10-062028-10-06Us
US7981938No2008-10-062028-10-06Us
US8093296No2008-10-062028-10-06Us
US8093297No2008-10-062028-10-06Us
US8093298No2008-10-062028-10-06Us
US8097655No2008-10-062028-10-06Us
US8415395No2008-10-062028-10-06Us
US8415396No2008-10-062028-10-06Us
US8440721No2009-02-172029-02-17Us
US8440722No2009-02-172029-02-17Us
US8927607No2013-08-222033-08-22Us
US9399036No2013-08-222033-08-22Us
US9675613No2013-08-222033-08-22Us
US9555029No2013-08-222033-08-22Us
US9789108No2013-08-222033-08-22Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)156 °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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Download (2.96 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0000900000-c73c5a28a750cece607a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0049400000-2a76bd81d41e1bc5925c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0gba-0091000000-fb24bc910ffe7bd74811

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Hydrocarbon derivatives
Class
Tropones
Sub Class
Not Available
Direct Parent
Tropones
Alternative Parents
Anisoles / Alkyl aryl ethers / Cyclic ketones / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
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
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
aromatic ether, alkaloid, acetamides, carbotricyclic compound (CHEBI:23359) / an alkaloid (CPD-9785)

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
Uniprot Name
Tubulin beta-1 chain
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
Uniprot Name
Tubulin beta chain
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

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
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]
  2. Dvorak Z, Ulrichova J, Modriansky M, Maurel P: Effect of colchicine and its derivatives on the expression of selected isoforms of cytochrome P450 in primary cultures of human hepatocytes. Acta Univ Palacki Olomuc Fac Med. 2000;143:47-50. [PubMed:11144118]
  3. Tateishi T, Soucek P, Caraco Y, Guengerich FP, Wood AJ: Colchicine biotransformation by human liver microsomes. Identification of CYP3A4 as the major isoform responsible for colchicine demethylation. Biochem Pharmacol. 1997 Jan 10;53(1):111-6. [PubMed:8960070]
  4. Dvorak Z, Modriansky M, Pichard-Garcia L, Balaguer P, Vilarem MJ, Ulrichova J, Maurel P, Pascussi JM: Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9. doi: 10.1124/mol.64.1.160. [PubMed:12815172]
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 un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
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
Inhibitor
Inducer
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 un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
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]
  2. Dvorak Z, Modriansky M, Pichard-Garcia L, Balaguer P, Vilarem MJ, Ulrichova J, Maurel P, Pascussi JM: Colchicine down-regulates cytochrome P450 2B6, 2C8, 2C9, and 3A4 in human hepatocytes by affecting their glucocorticoid receptor-mediated regulation. Mol Pharmacol. 2003 Jul;64(1):160-9. doi: 10.1124/mol.64.1.160. [PubMed:12815172]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
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 ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
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]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [PubMed:11996015]

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 ...
Gene Name
ABCB4
Uniprot ID
P21439
Uniprot Name
Phosphatidylcholine translocator ABCB4
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
Uniprot Name
Solute carrier family 22 member 3
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
Substrate
Inhibitor
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
Uniprot Name
Multidrug resistance protein 1
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, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
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]

Drug created on July 08, 2007 11:02 / Updated on September 25, 2018 17:45