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Identification
NameImatinib
Accession NumberDB00619  (APRD01028, EXPT02967, DB03261)
TypeSmall Molecule
GroupsApproved
Description

Imatinib is a small molecule kinase inhibitor used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia) as its mesylate salt, imatinib mesilate (INN). It is occasionally referred to as CGP57148B or STI571 (especially in older publications). It is used in treating chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies.

It is the first member of a new class of agents that act by inhibiting particular tyrosine kinase enzymes, instead of non-specifically inhibiting rapidly dividing cells.

Structure
Thumb
Synonyms
4-(4-METHYL-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide
alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-P-toluidide
Imatinib
Imatinib Methansulfonate
Imatinibum
STI 571
External Identifiers
  • CGP-57148B
  • STI-571
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act Imatinibtablet400 mgoralActavis Pharma Company2014-04-29Not applicableCanada
Act Imatinibtablet100 mgoralActavis Pharma Company2014-04-29Not applicableCanada
Gleevectablet100 mg/1oralNovartis Pharmaceuticals Corporation2001-05-15Not applicableUs
Gleevectablet400 mgoralNovartis Pharmaceuticals Canada Inc2004-10-25Not applicableCanada
Gleeveccapsule100 mgoralNovartis Pharmaceuticals Canada Inc2001-09-262008-09-24Canada
Gleevectablet100 mgoralNovartis Pharmaceuticals Canada Inc2005-04-05Not applicableCanada
Gleevectablet100 mg/1oralAvera Mc Kennan Hospital2015-03-01Not applicableUs
Gleevectablet100 mg/1oralNovartis Pharma Produktions Gmb H2001-05-15Not applicableUs
Gleevectablet400 mg/1oralNovartis Pharmaceuticals Corporation2014-12-23Not applicableUs
Gleevectablet400 mg/1oralNovartis Pharmaceuticals Corporation2001-05-15Not applicableUs
Mylan-imatinibtablet400 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Mylan-imatinibtablet100 mgoralMylan Pharmaceuticals UlcNot applicableNot applicableCanada
PMS-imatinibtablet400 mgoralPharmascience Inc2015-05-26Not applicableCanada
PMS-imatinibtablet100 mgoralPharmascience Inc2015-05-26Not applicableCanada
Ran-imatinibtablet400 mgoralRanbaxy Pharmaceuticals Canada Inc.Not applicableNot applicableCanada
Ran-imatinibtablet100 mgoralRanbaxy Pharmaceuticals Canada Inc.Not applicableNot applicableCanada
Teva-imatinibtablet400 mgoralTeva Canada Limited2013-05-22Not applicableCanada
Teva-imatinibtablet100 mgoralTeva Canada Limited2013-04-02Not applicableCanada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-imatinibtablet100 mgoralApotex Inc2013-04-19Not applicableCanada
Apo-imatinibtablet400 mgoralApotex Inc2013-04-19Not applicableCanada
Imatinib Mesylatetablet, film coated400 mg/1oralAmerican Health Packaging2016-02-15Not applicableUs
Imatinib Mesylatetablet, film coated100 mg/1oralAmerican Health Packaging2016-02-15Not applicableUs
Imatinib Mesylatetablet, film coated400 mg/1oralSun Pharma Global FZE2016-02-01Not applicableUs
Imatinib Mesylatetablet, film coated100 mg/1oralSun Pharma Global FZE2016-02-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
CelonibCelon
EnlivenOrion
GlivecNovartis
ImatibGrey Inversiones
MesylonibMiracalus
MitinabGlenmark
PlivatinibPliva
ShantinibShantha
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Imatinib Mesylate
Thumb
  • InChI Key: YLMAHDNUQAMNNX-UHFFFAOYSA-N
  • Monoisotopic Mass: 589.247123333
  • Average Mass: 589.708
DBSALT000098
Categories
UNIIBKJ8M8G5HI
CAS number152459-95-5
WeightAverage: 493.6027
Monoisotopic: 493.259008649
Chemical FormulaC29H31N7O
InChI KeyInChIKey=KTUFNOKKBVMGRW-UHFFFAOYSA-N
InChI
InChI=1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)
IUPAC Name
N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)-4-[(4-methylpiperazin-1-yl)methyl]benzamide
SMILES
CN1CCN(CC2=CC=C(C=C2)C(=O)NC2=CC(NC3=NC=CC(=N3)C3=CN=CC=C3)=C(C)C=C2)CC1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-phenylbenzamides. These are benzamides that are N-linked to a phenyl group via the carboxamide group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentN-phenylbenzamides
Alternative Parents
Substituents
  • N-phenylbenzamide
  • Pyridinylpyrimidine
  • N-arylamide
  • Diaminotoluene
  • Benzoic acid or derivatives
  • Aminotoluene
  • Phenylmethylamine
  • Benzylamine
  • Benzoyl
  • Aralkylamine
  • N-alkylpiperazine
  • N-methylpiperazine
  • Toluene
  • Pyrimidine
  • Pyridine
  • Piperazine
  • 1,4-diazinane
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), Ph+ acute lymphoblastic leukaemia, myelodysplastic/myeloproliferative diseases, aggressive systemic mastocytosis, hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST).
PharmacodynamicsImatinib is an antineoplastic agent used to treat chronic myelogenous leukemia. Imatinib is a 2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of Abl with Bcr (breakpoint cluster region), termed Bcr-Abl. As this is now a continuously active tyrosine kinase, Imatinib is used to decrease Bcr-Abl activity.
Mechanism of actionImatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the Bcr-Abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukemia (CML). It inhibits proliferation and induces apoptosis in Bcr-Abl positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia. Imatinib also inhibits the receptor tyrosine kinases for platelet derived growth factor (PDGF) and stem cell factor (SCF) - called c-kit. Imatinib was identified in the late 1990s by Dr Brian J. Druker. Its development is an excellent example of rational drug design. Soon after identification of the bcr-abl target, the search for an inhibitor began. Chemists used a high-throughput screen of chemical libraries to identify the molecule 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.
Related Articles
AbsorptionThe pharmacokinetics in CML and GIST patients are similar. Imatinib is well absorbed with mean absolute bioavailability is 98% and maximum plasma levels achieved within 2-4 hours of dosing
Volume of distributionNot Available
Protein binding95% protein bound, mostly to albumin and alpha-1-acid glycoprotein.
Metabolism

Primarily hepatic via CYP3A4. Other cytochrome P450 enzymes, such as CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play a minor role in its metabolism. The main circulating active metabolite in humans is the N-demethylated piperazine derivative, formed predominantly by CYP3A4. This metabolite is similar in potency to the parent compound.

SubstrateEnzymesProduct
Imatinib
N-desmethylimatinib (CGP74588)Details
Imatinib
AFN911Details
Imatinib
CGP71422Details
Imatinib
CGP72383Details
Imatinib
Not Available
n-demethylated piperazineDetails
Route of eliminationImatinib elimination is predominately in the feces, mostly as metabolites. 81% of the dose is eliminated within 7 days, in feces (68% of the dose) and urine (13% of the dose). Unchanged imatinib accounted for 25% of the dose (5% urine, 20% faces), the remainder being metabolites.
Half lifeFollowing oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-demethyl derivative (CGP74588) are approximately 18 and 40 hours, respectively.
Clearance
  • 8 L/h [50-year-old CML and GIST patient weighing 50 kg]
  • 14 L/h [50-year-old CML and GIST patient weighing 100 kg]
ToxicityThe most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.
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+0.9865
Blood Brain Barrier+0.7624
Caco-2 permeable+0.5076
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.8107
P-glycoprotein inhibitor IINon-inhibitor0.5326
Renal organic cation transporterInhibitor0.5299
CYP450 2C9 substrateNon-substrate0.8287
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6547
CYP450 1A2 substrateNon-inhibitor0.6602
CYP450 2C9 inhibitorNon-inhibitor0.8813
CYP450 2D6 inhibitorNon-inhibitor0.7933
CYP450 2C19 inhibitorNon-inhibitor0.8516
CYP450 3A4 inhibitorNon-inhibitor0.9313
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7962
Ames testNon AMES toxic0.8134
CarcinogenicityNon-carcinogens0.919
BiodegradationNot ready biodegradable0.9819
Rat acute toxicity2.6013 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7709
hERG inhibition (predictor II)Inhibitor0.8887
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
Capsuleoral100 mg
Tabletoral100 mg/1
Tabletoral100 mg
Tabletoral400 mg
Tabletoral400 mg/1
Tablet, film coatedoral100 mg/1
Tablet, film coatedoral400 mg/1
Prices
Unit descriptionCostUnit
Gleevec 400 mg tablet174.38USD tablet
Gleevec 100 mg tablet41.69USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2093203 No2002-11-262013-04-01Canada
US5521184 Yes1995-07-042015-07-04Us
US6894051 Yes1999-11-232019-11-23Us
US6958335 Yes2002-06-192022-06-19Us
US7544799 Yes1999-01-162019-01-16Us
USRE43932 Yes1999-01-162019-01-16Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point226 °C (mesylate salt)Not Available
water solubilityVery soluble in water at pH < 5.5 (mesylate salt)Not Available
logP3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0146 mg/mLALOGPS
logP3.47ALOGPS
logP4.38ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)12.45ChemAxon
pKa (Strongest Basic)8.27ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.28 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity148.93 m3·mol-1ChemAxon
Polarizability55.54 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5521184
General References
  1. Deininger MW, Druker BJ: Specific targeted therapy of chronic myelogenous leukemia with imatinib. Pharmacol Rev. 2003 Sep;55(3):401-23. Epub 2003 Jul 17. [PubMed:12869662 ]
  2. Vigneri P, Wang JY: Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase. Nat Med. 2001 Feb;7(2):228-34. [PubMed:11175855 ]
  3. Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL: Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial. Cancer. 2006 Jul 15;107(2):345-51. [PubMed:16779792 ]
  4. Lassila M, Allen TJ, Cao Z, Thallas V, Jandeleit-Dahm KA, Candido R, Cooper ME: Imatinib attenuates diabetes-associated atherosclerosis. Arterioscler Thromb Vasc Biol. 2004 May;24(5):935-42. Epub 2004 Feb 26. [PubMed:14988091 ]
  5. Reeves PM, Bommarius B, Lebeis S, McNulty S, Christensen J, Swimm A, Chahroudi A, Chavan R, Feinberg MB, Veach D, Bornmann W, Sherman M, Kalman D: Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases. Nat Med. 2005 Jul;11(7):731-9. Epub 2005 Jun 26. [PubMed:15980865 ]
External Links
ATC CodesL01XE01
AHFS Codes
  • 10:00.00
  • 92:00.00
PDB Entries
FDA labelDownload (129 KB)
MSDSDownload (217 KB)
Interactions
Drug Interactions
Drug
AcetaminophenAcetaminophen may increase the hepatotoxic activities of Imatinib.
ApixabanThe serum concentration of Apixaban can be increased when it is combined with Imatinib.
AprepitantThe serum concentration of Imatinib can be increased when it is combined with Aprepitant.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Imatinib.
AtazanavirThe serum concentration of Imatinib can be increased when it is combined with Atazanavir.
AvanafilThe serum concentration of Avanafil can be increased when it is combined with Imatinib.
BexaroteneThe serum concentration of Imatinib can be decreased when it is combined with Bexarotene.
BoceprevirThe serum concentration of Imatinib can be increased when it is combined with Boceprevir.
BosentanThe serum concentration of Imatinib can be decreased when it is combined with Bosentan.
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Imatinib.
BrexpiprazoleThe serum concentration of Brexpiprazole can be increased when it is combined with Imatinib.
BudesonideThe serum concentration of Budesonide can be increased when it is combined with Imatinib.
CarbamazepineThe serum concentration of Imatinib can be decreased when it is combined with Carbamazepine.
CeritinibThe serum concentration of Imatinib can be increased when it is combined with Ceritinib.
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Imatinib.
ClarithromycinThe serum concentration of Imatinib can be increased when it is combined with Clarithromycin.
ClozapineThe risk or severity of adverse effects can be increased when Imatinib is combined with Clozapine.
CobicistatThe serum concentration of Imatinib can be increased when it is combined with Cobicistat.
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Imatinib.
ConivaptanThe serum concentration of Imatinib can be increased when it is combined with Conivaptan.
CrizotinibThe serum concentration of Imatinib can be increased when it is combined with Crizotinib.
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Imatinib.
DabrafenibThe serum concentration of Imatinib can be decreased when it is combined with Dabrafenib.
DapoxetineThe serum concentration of Dapoxetine can be increased when it is combined with Imatinib.
DarunavirThe serum concentration of Imatinib can be increased when it is combined with Darunavir.
DeferasiroxThe serum concentration of Imatinib can be decreased when it is combined with Deferasirox.
DelavirdineThe serum concentration of Imatinib can be increased when it is combined with Delavirdine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Imatinib.
DexamethasoneThe serum concentration of Imatinib can be decreased when it is combined with Dexamethasone.
DiltiazemThe serum concentration of Imatinib can be increased when it is combined with Diltiazem.
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Imatinib.
DomperidoneThe serum concentration of Domperidone can be increased when it is combined with Imatinib.
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Imatinib.
DronabinolThe serum concentration of Dronabinol can be increased when it is combined with Imatinib.
DronedaroneThe serum concentration of Imatinib can be increased when it is combined with Dronedarone.
EletriptanThe serum concentration of Eletriptan can be increased when it is combined with Imatinib.
EliglustatThe serum concentration of Eliglustat can be increased when it is combined with Imatinib.
EnzalutamideThe serum concentration of Imatinib can be decreased when it is combined with Enzalutamide.
EplerenoneThe serum concentration of Eplerenone can be increased when it is combined with Imatinib.
ErythromycinThe serum concentration of Imatinib can be increased when it is combined with Erythromycin.
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Imatinib.
FentanylThe serum concentration of Fentanyl can be increased when it is combined with Imatinib.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Imatinib.
FluconazoleThe serum concentration of Imatinib can be increased when it is combined with Fluconazole.
FludarabineImatinib may decrease the myelosuppressive activities of Fludarabine.
FlunisolideThe metabolism of Flunisolide can be decreased when combined with Imatinib.
FosamprenavirThe serum concentration of Imatinib can be increased when it is combined with Fosamprenavir.
FosphenytoinThe serum concentration of Imatinib can be decreased when it is combined with Fosphenytoin.
GemfibrozilThe serum concentration of the active metabolites of Imatinib can be reduced when Imatinib is used in combination with Gemfibrozil resulting in a loss in efficacy.
HalofantrineThe serum concentration of Halofantrine can be increased when it is combined with Imatinib.
HydrocodoneThe serum concentration of Hydrocodone can be increased when it is combined with Imatinib.
IbrutinibThe serum concentration of Ibrutinib can be increased when it is combined with Imatinib.
IbuprofenThe serum concentration of Imatinib can be decreased when it is combined with Ibuprofen.
IdelalisibThe serum concentration of Imatinib can be increased when it is combined with Idelalisib.
IfosfamideThe serum concentration of the active metabolites of Ifosfamide can be reduced when Ifosfamide is used in combination with Imatinib resulting in a loss in efficacy.
IndinavirThe serum concentration of Imatinib can be increased when it is combined with Indinavir.
IsavuconazoniumThe serum concentration of Imatinib can be increased when it is combined with Isavuconazonium.
ItraconazoleThe serum concentration of Imatinib can be increased when it is combined with Itraconazole.
IvabradineThe serum concentration of Ivabradine can be increased when it is combined with Imatinib.
IvacaftorThe serum concentration of Ivacaftor can be increased when it is combined with Imatinib.
KetoconazoleThe serum concentration of Imatinib can be increased when it is combined with Ketoconazole.
LansoprazoleLansoprazole may increase the dermatologic adverse activities of Imatinib.
LeflunomideThe risk or severity of adverse effects can be increased when Imatinib is combined with Leflunomide.
LomitapideThe serum concentration of Lomitapide can be increased when it is combined with Imatinib.
LurasidoneThe serum concentration of Lurasidone can be increased when it is combined with Imatinib.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Imatinib.
MifepristoneThe serum concentration of Imatinib can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Imatinib can be decreased when it is combined with Mitotane.
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Imatinib.
NatalizumabThe risk or severity of adverse effects can be increased when Imatinib is combined with Natalizumab.
NefazodoneThe serum concentration of Imatinib can be increased when it is combined with Nefazodone.
NelfinavirThe serum concentration of Imatinib can be increased when it is combined with Nelfinavir.
NilotinibThe serum concentration of Imatinib can be increased when it is combined with Nilotinib.
NimodipineThe serum concentration of Nimodipine can be increased when it is combined with Imatinib.
OlaparibThe serum concentration of Olaparib can be increased when it is combined with Imatinib.
OxycodoneThe risk or severity of adverse effects can be increased when Imatinib is combined with Oxycodone.
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Imatinib.
PhenobarbitalThe serum concentration of Imatinib can be decreased when it is combined with Phenobarbital.
PhenytoinThe serum concentration of Imatinib can be decreased when it is combined with Phenytoin.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Imatinib.
PimozideThe serum concentration of Pimozide can be increased when it is combined with Imatinib.
PosaconazoleThe serum concentration of Imatinib can be increased when it is combined with Posaconazole.
PrimidoneThe serum concentration of Imatinib can be decreased when it is combined with Primidone.
PropacetamolPropacetamol may increase the hepatotoxic activities of Imatinib.
PropafenoneThe serum concentration of Propafenone can be increased when it is combined with Imatinib.
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Imatinib.
RifabutinThe serum concentration of Imatinib can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Imatinib can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Imatinib can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Imatinib can be increased when it is combined with Ritonavir.
RoflumilastRoflumilast may increase the immunosuppressive activities of Imatinib.
SalmeterolThe serum concentration of Salmeterol can be increased when it is combined with Imatinib.
SaquinavirThe serum concentration of Imatinib can be increased when it is combined with Saquinavir.
SaxagliptinThe serum concentration of Saxagliptin can be increased when it is combined with Imatinib.
SiltuximabThe serum concentration of Imatinib can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Imatinib.
SimvastatinThe metabolism of Simvastatin can be decreased when combined with Imatinib.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Imatinib.
SonidegibThe serum concentration of Sonidegib can be increased when it is combined with Imatinib.
St. John's WortThe metabolism of Imatinib can be increased when combined with St. John&#39;s Wort.
SuvorexantThe serum concentration of Suvorexant can be increased when it is combined with Imatinib.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Imatinib.
TelaprevirThe serum concentration of Imatinib can be increased when it is combined with Telaprevir.
TelithromycinThe serum concentration of Imatinib can be increased when it is combined with Telithromycin.
TesmilifeneThe serum concentration of Imatinib can be decreased when it is combined with Tesmilifene.
TocilizumabThe serum concentration of Imatinib can be decreased when it is combined with Tocilizumab.
TofacitinibImatinib may increase the immunosuppressive activities of Tofacitinib.
TolvaptanThe serum concentration of Tolvaptan can be increased when it is combined with Imatinib.
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Imatinib.
TrabectedinThe serum concentration of Trabectedin can be increased when it is combined with Imatinib.
TrastuzumabTrastuzumab may increase the neutropenic activities of Imatinib.
UlipristalThe serum concentration of Ulipristal can be increased when it is combined with Imatinib.
VerapamilThe serum concentration of Imatinib can be increased when it is combined with Verapamil.
VilazodoneThe serum concentration of Vilazodone can be increased when it is combined with Imatinib.
VindesineThe serum concentration of Vindesine can be increased when it is combined with Imatinib.
VoriconazoleThe serum concentration of Imatinib can be increased when it is combined with Voriconazole.
WarfarinImatinib may increase the anticoagulant activities of Warfarin.
ZopicloneThe serum concentration of Zopiclone can be increased when it is combined with Imatinib.
ZuclopenthixolThe serum concentration of Zuclopenthixol can be increased when it is combined with Imatinib.
Food Interactions
  • Take with food to reduce the incidence of gastric irritation. Follow with a large glass of water. A lipid rich meal will slightly reduce and delay absorption. Avoid grapefruit and grapefruit juice throughout treatment, grapefruit can significantly increase serum levels of this product.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Protein serine/threonine kinase activity
Specific Function:
Not Available
Gene Name:
BCR/ABL fusion
Uniprot ID:
A9UF02
Molecular Weight:
179321.835 Da
References
  1. Nadal E, Olavarria E: Imatinib mesylate (Gleevec/Glivec) a molecular-targeted therapy for chronic myeloid leukaemia and other malignancies. Int J Clin Pract. 2004 May;58(5):511-6. [PubMed:15206509 ]
  2. Waller CF: Imatinib mesylate. Recent Results Cancer Res. 2010;184:3-20. doi: 10.1007/978-3-642-01222-8_1. [PubMed:20072827 ]
  3. Croom KF, Perry CM: Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs. 2003;63(5):513-22; discussion 523-4. [PubMed:12600228 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonistmultitarget
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1...
Gene Name:
KIT
Uniprot ID:
P10721
Molecular Weight:
109863.655 Da
References
  1. Lee JL, Kim JY, Ryu MH, Kang HJ, Chang HM, Kim TW, Lee H, Park JH, Kim HC, Kim JS, Kang YK: Response to imatinib in KIT- and PDGFRA-wild type gastrointestinal stromal associated with neurofibromatosis type 1. Dig Dis Sci. 2006 Jun;51(6):1043-6. [PubMed:16865565 ]
  2. Dy GK, Miller AA, Mandrekar SJ, Aubry MC, Langdon RM Jr, Morton RF, Schild SE, Jett JR, Adjei AA: A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Ann Oncol. 2005 Nov;16(11):1811-6. Epub 2005 Aug 8. [PubMed:16087693 ]
  3. Rutkowski P, Nowecki ZI, Debiec-Rychter M, Grzesiakowska U, Michej W, Wozniak A, Siedlecki JA, Limon J, vel Dobosz AJ, Kakol M, Osuch C, Ruka W: Predictive factors for long-term effects of imatinib therapy in patients with inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs). J Cancer Res Clin Oncol. 2007 Sep;133(9):589-97. Epub 2007 Apr 26. [PubMed:17458563 ]
  4. De Giorgi U: KIT mutations and imatinib dose effects in patients with gastrointestinal stromal tumors. J Clin Oncol. 2007 Mar 20;25(9):1146-7; author reply 1147-8. [PubMed:17369583 ]
  5. Posadas EM, Kwitkowski V, Kotz HL, Espina V, Minasian L, Tchabo N, Premkumar A, Hussain MM, Chang R, Steinberg SM, Kohn EC: A prospective analysis of imatinib-induced c-KIT modulation in ovarian cancer: a phase II clinical study with proteomic profiling. Cancer. 2007 Jul 15;110(2):309-17. [PubMed:17559139 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
RET
Uniprot ID:
O43519
Molecular Weight:
2129.3 Da
References
  1. de Groot JW, Plaza Menacho I, Schepers H, Drenth-Diephuis LJ, Osinga J, Plukker JT, Links TP, Eggen BJ, Hofstra RM: Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery. 2006 Jun;139(6):806-14. [PubMed:16782438 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Receptor tyrosine kinase involved in the development and the maturation of the central and peripheral nervous systems through regulation of proliferation, differentiation and survival of sympathetic and nervous neurons. High affinity receptor for NGF which is its primary ligand, it can also bind and be activated by NTF3/neurotrophin-3. However, NTF3 only supports axonal extension through NTRK1 ...
Gene Name:
NTRK1
Uniprot ID:
P04629
Molecular Weight:
87496.465 Da
References
  1. Catani M, De Milito R, Simi M: [New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location]. Chir Ital. 2005 Jan-Feb;57(1):127-33. [PubMed:15832750 ]
  2. Kovacs M, Nagy P, Pak G, Feher J: [Gastrointestinal stromal tumors (GISTs): clinical and pathological features]. Orv Hetil. 2005 Jun 26;146(26):1375-81. [PubMed:16052979 ]
  3. de Groot JW, Plaza Menacho I, Schepers H, Drenth-Diephuis LJ, Osinga J, Plukker JT, Links TP, Eggen BJ, Hofstra RM: Cellular effects of imatinib on medullary thyroid cancer cells harboring multiple endocrine neoplasia Type 2A and 2B associated RET mutations. Surgery. 2006 Jun;139(6):806-14. [PubMed:16782438 ]
  4. de Groot JW, Zonnenberg BA, van Ufford-Mannesse PQ, de Vries MM, Links TP, Lips CJ, Voest EE: A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2007 Sep;92(9):3466-9. Epub 2007 Jun 19. [PubMed:17579194 ]
  5. Delbaldo C: [Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)]. Therapie. 2007 Mar-Apr;62(2):87-90. Epub 2007 Jun 21. [PubMed:17582306 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Protein homodimerization activity
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in inn...
Gene Name:
CSF1R
Uniprot ID:
P07333
Molecular Weight:
107982.955 Da
References
  1. Dewar AL, Zannettino AC, Hughes TP, Lyons AB: Inhibition of c-fms by imatinib: expanding the spectrum of treatment. Cell Cycle. 2005 Jul;4(7):851-3. Epub 2005 Jul 28. [PubMed:15917650 ]
  2. Taylor JR, Brownlow N, Domin J, Dibb NJ: FMS receptor for M-CSF (CSF-1) is sensitive to the kinase inhibitor imatinib and mutation of Asp-802 to Val confers resistance. Oncogene. 2006 Jan 5;25(1):147-51. [PubMed:16170366 ]
  3. Dewar AL, Farrugia AN, Condina MR, Bik To L, Hughes TP, Vernon-Roberts B, Zannettino AC: Imatinib as a potential antiresorptive therapy for bone disease. Blood. 2006 Jun 1;107(11):4334-7. Epub 2006 Jan 31. [PubMed:16449525 ]
  4. Ando W, Hashimoto J, Nampei A, Tsuboi H, Tateishi K, Ono T, Nakamura N, Ochi T, Yoshikawa H: Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA). J Bone Miner Metab. 2006;24(4):274-82. [PubMed:16816921 ]
  5. El Hajj Dib I, Gallet M, Mentaverri R, Sevenet N, Brazier M, Kamel S: Imatinib mesylate (Gleevec) enhances mature osteoclast apoptosis and suppresses osteoclast bone resorbing activity. Eur J Pharmacol. 2006 Dec 3;551(1-3):27-33. Epub 2006 Sep 16. [PubMed:17049513 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Vascular endothelial growth factor-activated receptor activity
Specific Function:
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for...
Gene Name:
PDGFRA
Uniprot ID:
P16234
Molecular Weight:
122668.46 Da
References
  1. Yi ES, Strong CR, Piao Z, Perucho M, Weidner N: Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity. Appl Immunohistochem Mol Morphol. 2005 Jun;13(2):157-61. [PubMed:15894928 ]
  2. Borbenyi Z: [Disorders with eosinophilia, treatment of hypereosinophilic syndrome]. Orv Hetil. 2005 May 1;146(18 Suppl 1):911-6. [PubMed:15921304 ]
  3. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC: PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005 Aug 10;23(23):5357-64. Epub 2005 May 31. [PubMed:15928335 ]
  4. Chen LL, Sabripour M, Andtbacka RH, Patel SR, Feig BW, Macapinlac HA, Choi H, Wu EF, Frazier ML, Benjamin RS: Imatinib resistance in gastrointestinal stromal tumors. Curr Oncol Rep. 2005 Jul;7(4):293-9. [PubMed:15946589 ]
  5. Tefferi A: Modern diagnosis and treatment of primary eosinophilia. Acta Haematol. 2005;114(1):52-60. [PubMed:15995325 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Transmembrane receptor protein tyrosine kinase activity
Specific Function:
Tyrosine kinase that functions as cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular mat...
Gene Name:
DDR1
Uniprot ID:
Q08345
Molecular Weight:
101126.72 Da
References
  1. Gotlib J, Berube C, Growney JD, Chen CC, George TI, Williams C, Kajiguchi T, Ruan J, Lilleberg SL, Durocher JA, Lichy JH, Wang Y, Cohen PS, Arber DA, Heinrich MC, Neckers L, Galli SJ, Gilliland DG, Coutre SE: Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation. Blood. 2005 Oct 15;106(8):2865-70. Epub 2005 Jun 21. [PubMed:15972446 ]
  2. Xu L, Tong R, Cochran DM, Jain RK: Blocking platelet-derived growth factor-D/platelet-derived growth factor receptor beta signaling inhibits human renal cell carcinoma progression in an orthotopic mouse model. Cancer Res. 2005 Jul 1;65(13):5711-9. [PubMed:15994946 ]
  3. Neef M, Ledermann M, Saegesser H, Schneider V, Widmer N, Decosterd LA, Rochat B, Reichen J: Oral imatinib treatment reduces early fibrogenesis but does not prevent progression in the long term. J Hepatol. 2006 Jan;44(1):167-75. Epub 2005 Jul 12. [PubMed:16168515 ]
  4. Jubert C, Geoerger B, Grill J, Hartmann O, Vassal G: [Targeted therapies in pediatric oncology: a new therapeutic approach?]. Arch Pediatr. 2006 Feb;13(2):189-94. Epub 2005 Nov 17. [PubMed:16298518 ]
  5. Benjamin RS, Blanke CD, Blay JY, Bonvalot S, Eisenberg B: Management of gastrointestinal stromal tumors in the imatinib era: selected case studies. Oncologist. 2006 Jan;11(1):9-20. [PubMed:16401709 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Syntaxin binding
Specific Function:
Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 ...
Gene Name:
ABL1
Uniprot ID:
P00519
Molecular Weight:
122871.435 Da
References
  1. Hoerth E, Kodym R: Involvment of c-Abl in the radiation-induced inhibition of myoblast differentiation. Int J Radiat Biol. 2004 Oct;80(10):729-36. [PubMed:15799618 ]
  2. Dewar AL, Zannettino AC, Hughes TP, Lyons AB: Inhibition of c-fms by imatinib: expanding the spectrum of treatment. Cell Cycle. 2005 Jul;4(7):851-3. Epub 2005 Jul 28. [PubMed:15917650 ]
  3. Agirre X, Roman-Gomez J, Vazquez I, Jimenez-Velasco A, Larrayoz MJ, Lahortiga I, Andreu EJ, Marquez J, Beltran de Heredia JM, Odero MD, Prosper F, Calasanz MJ: Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2 (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to imatinib. Cancer Genet Cytogenet. 2005 Jul 1;160(1):22-6. [PubMed:15949566 ]
  4. Brueggemeier SB, Wu D, Kron SJ, Palecek SP: Protein-acrylamide copolymer hydrogels for array-based detection of tyrosine kinase activity from cell lysates. Biomacromolecules. 2005 Sep-Oct;6(5):2765-75. [PubMed:16153117 ]
  5. Haberler C, Gelpi E, Marosi C, Rossler K, Birner P, Budka H, Hainfellner JA: Immunohistochemical analysis of platelet-derived growth factor receptor-alpha, -beta, c-kit, c-abl, and arg proteins in glioblastoma: possible implications for patient selection for imatinib mesylate therapy. J Neurooncol. 2006 Jan;76(2):105-9. [PubMed:16205964 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Vascular endothelial growth factor binding
Specific Function:
Tyrosine-protein kinase that acts as cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, survival, differentiation, chemotaxis and migration. Plays an essential role in blood vessel development by promoting proliferation, migration and recruitment of peri...
Gene Name:
PDGFRB
Uniprot ID:
P09619
Molecular Weight:
123966.895 Da
References
  1. Basciani S, Brama M, Mariani S, De Luca G, Arizzi M, Vesci L, Pisano C, Dolci S, Spera G, Gnessi L: Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity. Cancer Res. 2005 Mar 1;65(5):1897-903. [PubMed:15753388 ]
  2. Jones RL, Judson IR: The development and application of imatinib. Expert Opin Drug Saf. 2005 Mar;4(2):183-91. [PubMed:15794712 ]
  3. Modi S, Seidman AD, Dickler M, Moasser M, D'Andrea G, Moynahan ME, Menell J, Panageas KS, Tan LK, Norton L, Hudis CA: A phase II trial of imatinib mesylate monotherapy in patients with metastatic breast cancer. Breast Cancer Res Treat. 2005 Mar;90(2):157-63. [PubMed:15803362 ]
  4. Johnson FM, Saigal B, Donato NJ: Induction of heparin-binding EGF-like growth factor and activation of EGF receptor in imatinib mesylate-treated squamous carcinoma cells. J Cell Physiol. 2005 Nov;205(2):218-27. [PubMed:15887238 ]
  5. Chen J, Rocken C, Nitsche B, Hosius C, Gschaidmeier H, Kahl S, Malfertheiner P, Ebert MP: The tyrosine kinase inhibitor imatinib fails to inhibit pancreatic cancer progression. Cancer Lett. 2006 Feb 28;233(2):328-37. [PubMed:15893416 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. 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 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxygen binding
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
  2. 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 ]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Oxygen binding
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.
Gene Name:
CYP3A7
Uniprot ID:
P24462
Molecular Weight:
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N...
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular Weight:
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423 ]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
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. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
References
  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. FDA label
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Not Available
Specific Function:
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. FDA label

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
References
  1. Davies A, Jordanides NE, Giannoudis A, Lucas CM, Hatziieremia S, Harris RJ, Jorgensen HG, Holyoake TL, Pirmohamed M, Clark RE, Mountford JC: Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009 Nov;23(11):1999-2006. doi: 10.1038/leu.2009.166. Epub 2009 Aug 27. [PubMed:19710702 ]
  2. Engler JR, Frede A, Saunders VA, Zannettino AC, Hughes TP, White DL: Chronic myeloid leukemia CD34+ cells have reduced uptake of imatinib due to low OCT-1 activity. Leukemia. 2010 Apr;24(4):765-70. doi: 10.1038/leu.2010.16. Epub 2010 Feb 11. [PubMed:20147974 ]
  3. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [PubMed:18788725 ]
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. Davies A, Jordanides NE, Giannoudis A, Lucas CM, Hatziieremia S, Harris RJ, Jorgensen HG, Holyoake TL, Pirmohamed M, Clark RE, Mountford JC: Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009 Nov;23(11):1999-2006. doi: 10.1038/leu.2009.166. Epub 2009 Aug 27. [PubMed:19710702 ]
  2. Dohse M, Scharenberg C, Shukla S, Robey RW, Volkmann T, Deeken JF, Brendel C, Ambudkar SV, Neubauer A, Bates SE: Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib. Drug Metab Dispos. 2010 Aug;38(8):1371-80. doi: 10.1124/dmd.109.031302. Epub 2010 Apr 27. [PubMed:20423956 ]
  3. Hamada A, Miyano H, Watanabe H, Saito H: Interaction of imatinib mesilate with human P-glycoprotein. J Pharmacol Exp Ther. 2003 Nov;307(2):824-8. Epub 2003 Sep 15. [PubMed:12975485 ]
  4. Thomas J, Wang L, Clark RE, Pirmohamed M: Active transport of imatinib into and out of cells: implications for drug resistance. Blood. 2004 Dec 1;104(12):3739-45. Epub 2004 Aug 17. [PubMed:15315971 ]
  5. Hegedus C, Ozvegy-Laczka C, Apati A, Magocsi M, Nemet K, Orfi L, Keri G, Katona M, Takats Z, Varadi A, Szakacs G, Sarkadi B: Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662 ]
  6. Giannoudis A, Davies A, Lucas CM, Harris RJ, Pirmohamed M, Clark RE: Effective dasatinib uptake may occur without human organic cation transporter 1 (hOCT1): implications for the treatment of imatinib-resistant chronic myeloid leukemia. Blood. 2008 Oct 15;112(8):3348-54. doi: 10.1182/blood-2007-10-116236. Epub 2008 Jul 31. [PubMed:18669873 ]
  7. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, Schellens JH: The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005 Apr 1;65(7):2577-82. [PubMed:15805252 ]
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters]. Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [PubMed:15918555 ]
  9. Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, de Boeck G, Sparreboom A, Verweij J, Nooter K: Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52. Epub 2005 Jul 9. [PubMed:15970668 ]
  10. Galimberti S, Cervetti G, Guerrini F, Testi R, Pacini S, Fazzi R, Simi P, Petrini M: Quantitative molecular monitoring of BCR-ABL and MDR1 transcripts in patients with chronic myeloid leukemia during Imatinib treatment. Cancer Genet Cytogenet. 2005 Oct 1;162(1):57-62. [PubMed:16157201 ]
  11. Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, Prenen H, de Jong FA, Baker SD, Bates SE, Figg WD, Verweij J, Sparreboom A, Nooter K: Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006 Aug;80(2):192-201. [PubMed:16890580 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Quaternary ammonium group transmembrane transporter activity
Specific Function:
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...
Gene Name:
SLC22A2
Uniprot ID:
O15244
Molecular Weight:
62579.99 Da
References
  1. Tanihara Y, Masuda S, Katsura T, Inui K: Protective effect of concomitant administration of imatinib on cisplatin-induced nephrotoxicity focusing on renal organic cation transporter OCT2. Biochem Pharmacol. 2009 Nov 1;78(9):1263-71. doi: 10.1016/j.bcp.2009.06.014. Epub 2009 Jun 18. [PubMed:19540211 ]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
References
  1. Houghton PJ, Germain GS, Harwood FC, Schuetz JD, Stewart CF, Buchdunger E, Traxler P: Imatinib mesylate is a potent inhibitor of the ABCG2 (BCRP) transporter and reverses resistance to topotecan and SN-38 in vitro. Cancer Res. 2004 Apr 1;64(7):2333-7. [PubMed:15059881 ]
  2. An Y, Ongkeko WM: ABCG2: the key to chemoresistance in cancer stem cells? Expert Opin Drug Metab Toxicol. 2009 Dec;5(12):1529-42. doi: 10.1517/17425250903228834. [PubMed:19708828 ]
  3. Davies A, Jordanides NE, Giannoudis A, Lucas CM, Hatziieremia S, Harris RJ, Jorgensen HG, Holyoake TL, Pirmohamed M, Clark RE, Mountford JC: Nilotinib concentration in cell lines and primary CD34(+) chronic myeloid leukemia cells is not mediated by active uptake or efflux by major drug transporters. Leukemia. 2009 Nov;23(11):1999-2006. doi: 10.1038/leu.2009.166. Epub 2009 Aug 27. [PubMed:19710702 ]
  4. Dohse M, Scharenberg C, Shukla S, Robey RW, Volkmann T, Deeken JF, Brendel C, Ambudkar SV, Neubauer A, Bates SE: Comparison of ATP-binding cassette transporter interactions with the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib. Drug Metab Dispos. 2010 Aug;38(8):1371-80. doi: 10.1124/dmd.109.031302. Epub 2010 Apr 27. [PubMed:20423956 ]
  5. Burger H, van Tol H, Boersma AW, Brok M, Wiemer EA, Stoter G, Nooter K: Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2. Epub 2004 Jul 13. [PubMed:15251980 ]
  6. Hegedus C, Ozvegy-Laczka C, Apati A, Magocsi M, Nemet K, Orfi L, Keri G, Katona M, Takats Z, Varadi A, Szakacs G, Sarkadi B: Interaction of nilotinib, dasatinib and bosutinib with ABCB1 and ABCG2: implications for altered anti-cancer effects and pharmacological properties. Br J Pharmacol. 2009 Oct;158(4):1153-64. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662 ]
  7. Breedveld P, Pluim D, Cipriani G, Wielinga P, van Tellingen O, Schinkel AH, Schellens JH: The effect of Bcrp1 (Abcg2) on the in vivo pharmacokinetics and brain penetration of imatinib mesylate (Gleevec): implications for the use of breast cancer resistance protein and P-glycoprotein inhibitors to enable the brain penetration of imatinib in patients. Cancer Res. 2005 Apr 1;65(7):2577-82. [PubMed:15805252 ]
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters]. Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [PubMed:15918555 ]
  9. Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, de Boeck G, Sparreboom A, Verweij J, Nooter K: Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005 Jul;4(7):747-52. Epub 2005 Jul 9. [PubMed:15970668 ]
  10. Yanase K, Tsukahara S, Mitsuhashi J, Sugimoto Y: Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. Cancer Lett. 2006 Mar 8;234(1):73-80. Epub 2005 Nov 21. [PubMed:16303243 ]
  11. Nakanishi T, Shiozawa K, Hassel BA, Ross DD: Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib-induced reduction of BCRP expression. Blood. 2006 Jul 15;108(2):678-84. Epub 2006 Mar 16. [PubMed:16543472 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Transporter activity
Specific Function:
Plays an important role in the formation of pulmonary surfactant, probably by transporting lipids such as cholesterol.
Gene Name:
ABCA3
Uniprot ID:
Q99758
Molecular Weight:
191360.235 Da
References
  1. Chapuy B, Panse M, Radunski U, Koch R, Wenzel D, Inagaki N, Haase D, Truemper L, Wulf GG: ABC transporter A3 facilitates lysosomal sequestration of imatinib and modulates susceptibility of chronic myeloid leukemia cell lines to this drug. Haematologica. 2009 Nov;94(11):1528-36. doi: 10.3324/haematol.2009.008631. [PubMed:19880777 ]
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Drug created on June 13, 2005 07:24 / Updated on May 24, 2016 03:10