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Identification
NameImatinib
Accession NumberDB00619  (APRD01028, DB03261, EXPT02967)
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
SynonymLanguageCode
4-(4-METHYL-piperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamideNot AvailableNot Available
alpha-(4-Methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-P-toluidideNot AvailableNot Available
ImatinibFrench/German/SpanishINN
Imatinib MethansulfonateNot AvailableNot Available
ImatinibumLatinINN
STI 571Not AvailableNot Available
Salts
Name/CAS Structure Properties
Imatinib Mesylate
Thumb
  • InChI Key: YLMAHDNUQAMNNX-UHFFFAOYSA-N
  • Monoisotopic Mass: 589.247123333
  • Average Mass: 589.708
DBSALT000098
Brand names
NameCompany
CelonibCelon
EnlivenOrion
GleevecNovartis
GlivecNovartis
ImatibGrey Inversiones
MesylonibMiracalus
MitinabGlenmark
PlivatinibPliva
ShantinibShantha
Brand mixturesNot Available
Categories
CAS number152459-95-5
WeightAverage: 493.6027
Monoisotopic: 493.259008649
Chemical FormulaC29H31N7O
InChI KeyKTUFNOKKBVMGRW-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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzamides
Direct parentN-phenylbenzamides
Alternative parentsPyridinylpyrimidines; Anilides; Benzoyl Derivatives; Toluenes; Diazinanes; Pyridines and Derivatives; Piperazines; Tertiary Amines; Secondary Carboxylic Acid Amides; Enolates; Carboxylic Acids; Secondary Amines; Polyamines
Substituentspyridinylpyrimidine; acetanilide; benzoyl; toluene; 1,4-diazinane; pyridine; piperazine; pyrimidine; secondary carboxylic acid amide; tertiary amine; carboxamide group; secondary amine; polyamine; enolate; carboxylic acid derivative; carboxylic acid; organonitrogen compound; amine
Classification descriptionThis compound belongs to the n-phenylbenzamides.
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.
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
Property Value Probability
Human Intestinal Absorption + 0.9865
Blood Brain Barrier + 0.7624
Caco-2 permeable + 0.5076
P-glycoprotein substrate Substrate 0.7863
P-glycoprotein inhibitor I Inhibitor 0.8107
P-glycoprotein inhibitor II Non-inhibitor 0.5326
Renal organic cation transporter Inhibitor 0.5299
CYP450 2C9 substrate Non-substrate 0.8287
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6547
CYP450 1A2 substrate Non-inhibitor 0.6602
CYP450 2C9 substrate Non-inhibitor 0.8813
CYP450 2D6 substrate Non-inhibitor 0.7933
CYP450 2C19 substrate Non-inhibitor 0.8516
CYP450 3A4 substrate Non-inhibitor 0.9313
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7962
Ames test Non AMES toxic 0.8134
Carcinogenicity Non-carcinogens 0.919
Biodegradation Not ready biodegradable 0.9819
Rat acute toxicity 2.6013 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7709
hERG inhibition (predictor II) Inhibitor 0.8887
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
TabletOral100 mg, 400 mg
Prices
Unit descriptionCostUnit
Gleevec 400 mg tablet174.38USDtablet
Gleevec 100 mg tablet41.69USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States69583352002-06-192022-06-19
United States55211841995-01-042015-01-04
Canada20932032002-11-262013-04-01
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 Solubility0.0146ALOGPS
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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US5521184
General Reference
  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
  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
  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
  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
  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
External Links
ResourceLink
KEGG DrugD01441
PubChem Compound5291
PubChem Substance46505055
ChemSpider5101
BindingDB13530
ChEBI45783
ChEMBLCHEMBL941
Therapeutic Targets DatabaseDNC001383
PharmGKBPA10804
HETSTI
Drug Product Database2253283
RxListhttp://www.rxlist.com/cgi/generic3/gleevec.htm
Drugs.comhttp://www.drugs.com/cdi/imatinib.html
WikipediaImatinib
ATC CodesL01XE01
AHFS Codes
  • 10:00.00
  • 92:00.00
PDB Entries
FDA labelshow(129 KB)
MSDSshow(217 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolImatinib may increase the anticoagulant effect of acenocoumarol.
AcetaminophenIncreased hepatic toxicity of both agents
AnisindioneImatinib may increase the anticoagulant effect of anisindione.
AprepitantAprepitant may change levels of the chemotherapy agent, imatinib.
AtorvastatinImatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if imatinib is initiated, discontinued or dose changed.
BromazepamImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of bromazepam by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of bromazepam if imatinib is initiated, discontinued or dose changed. Dosage adjustments may be required.
CarbamazepineCarbamazepine, a strong CYP3A4 inducer, may increase the metabolism of imatinib. Imatinib, a strong CYP3A4 inhibitor, may increase the metabolism of carbamazepine. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose changed.
CerivastatinImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of cerivastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cerivastatin if imatinib is initiated, discontinued or dose changed.
ClarithromycinThe macrolide, clarithromycin, may increase the serum concentration of imatinib.
CyclosporineImatinib increases the effect and toxicity of cyclosporine
DantroleneImatinib may increase the serum concentration of dantrolene by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dantrolene if imatinib is initiated, discontinued or dose changed.
DexamethasoneDexamethasone may decrease levels of imatinib.
DicoumarolImatinib may increase the anticoagulant effect of dicumarol.
ErythromycinThe macrolide, erythromycin, may increase the serum concentration of imatinib.
EthotoinThe hydantoin decreases the levels of imatinib
EtravirineImatinib, when used concomitantly with etravirine, may experience a decrease in serum concentration. It is recommended to avoid this combination if alternative are available. If concurrent use is not avoidable, it is recommended to increase the dosage of cabozantinib by a minimum of 50%, and to monitor therapy.
FosphenytoinThe hydantoin decreases the levels of imatinib
ItraconazoleItraconazole may increase the levels of imatinib.
JosamycinThe macrolide, josamycin, may increase the serum concentration of imatinib.
KetoconazoleKetoconazole may increase the levels of imatinib.
LovastatinImatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if imatinib is initiated, discontinued or dose changed.
LurasidoneConcomitant therapy with a strong CYP3A4 inhibitor will increase level or effect of lurasidone. Coadministration with lurasidone is contraindicated.
MephenytoinThe hydantoin decreases the levels of imatinib
NifedipineImatinib increases the effect and toxicity of nifedipine
PhenobarbitalPhenobarbital decreases levels of imatinib
PhenytoinThe hydantoin decreases the levels of imatinib
PimozideImatinib may increase the effect and toxicity of pimozide.
RifampicinRifampin decreases levels of imatinib
SimvastatinImatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if imatinib is initiated, discontinued or dose changed.
St. John's WortSt. John's Wort decreases levels of imatinib
TacrolimusThe strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tacrolimus, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Tacrolimus if Imatinib is initiated, discontinued or dose changed.
TadalafilImatinib may reduce the metabolism of Tadalafil. Concomitant therapy should be avoided if possible due to high risk of Tadalafil toxicity.
TamoxifenImatinib may increase the serum concentration of Tamoxifen by decreasing its metabolism and clearance. Imatinib may also decrease the therapeutic effect of Tamoxifen by decreasing active metabolite production. Monitor for changes in the therapeutic/adverse effects of Tamoxifen if Imatinib is initiated, discontinued or dose changed.
TamsulosinImatinib, a CYP3A4/2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4/2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Imatinib is initiated, discontinued, or dose changed.
TelithromycinCo-administration may result in altered plasma concentrations of Imatinib and/or Telithromycin. Consider alternate therapy or monitor the therapeutic/adverse effects of both agents.
TemsirolimusImatinib may inhibit the metabolism and clearance of Temsirolimus. Concomitant therapy should be avoided.
TeniposideThe strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Teniposide, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Teniposide if Imatinib is initiated, discontinued or dose changed.
TiagabineThe strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Tiagabine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Tiagabine if Imatinib is initiated, discontinued or dose changed.
TolterodineImatinib may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TopotecanThe BCRP/ABCG2 inhibitor, Imatinib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Imatinib is initiated, discontinued or dose changed.
TramadolImatinib may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance. Imatinib may decrease the effect of Tramadol by decreasing active metabolite production.
TrastuzumabTrastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
TrazodoneThe CYP3A4 inhibitor, Imatinib, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Consider alternate therapy or monitor for changes in Trazodone efficacy/toxicity if Imatinib is initiated, discontinued or dose changed.
TrimipramineThe strong CYP3A4 inhibitor, Imatinib, may decrease the metabolism and clearance of Trimipramine, a CYP3A4 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimipramine if Imatinib is initiated, discontinued or dose changed.
VardenafilImatinib, a strong CYP3A4 inhibitor, may reduce the metabolism and clearance of Vardenafil. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Vardenafil.
VenlafaxineImatinib, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Venlafaxine, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Venlafaxine if Imatinib is initiated, discontinued, or dose changed.
VerapamilImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Veramapil, a CYP3A4 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Verapamil if Imatinib is initiated, discontinued or dose changed.
VinblastineImatinib, a strong CYP3A4 inhibitor, may decrease the metabolism of Vinblastine. Consider alternate therapy to avoid Vinblastine toxicity. Monitor for changes in the therapeutic/adverse effects of Vinblastine if Imatinib is initiated, discontinued or dose changed.
VincristineImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vincristine by decreasing its metabolism. Consider alternate therapy to avoid Vincristine toxicity. Monitor for changes in the therapeutic and adverse effects of Vincristine if Imatinib is initiated, discontinued or dose changed.
VinorelbineImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of Vinorelbine by decreasing its metabolism. Consider alternate therapy to avoid Vinorelbine toxicity. Monitor for changes in the therapeutic and adverse effects of Vinorelbine if Imatinib is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of imatinib by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of imatinib if voriconazole is initiated, discontinued or dose changed.
WarfarinImatinib may increase the anticoagulant effect of warfarin increasing the risk of bleeding. Monitor for changes in prothrombin time and therapeutic and adverse effects of warfarin if imatinib is initiated, discontinued or dose changed.
ZonisamideImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zonisamide by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zonisamide if imatinib is initiated, discontinued or dose changed.
ZopicloneImatinib, a strong CYP3A4 inhibitor, may increase the serum concentration of zopiclone by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of zopiclone if imatinib is initiated, discontinued or dose changed.
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

1. BCR/ABL fusion protein isoform X9

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
BCR/ABL fusion protein isoform X9 A9UF02 Details

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
  2. Waller CF: Imatinib mesylate. Recent Results Cancer Res. 2010;184:3-20. Pubmed
  3. Croom KF, Perry CM: Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs. 2003;63(5):513-22; discussion 523-4. Pubmed

2. Mast/stem cell growth factor receptor Kit

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist multitarget

Components

Name UniProt ID Details
Mast/stem cell growth factor receptor Kit P10721 Details

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
  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
  3. Rutkowski P, Nowecki ZI, Debiec-Rychter M, Grzesiakowska U, Michej W, Wozniak A, Siedlecki JA, Limon J, 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
  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
  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

3. RET proto-oncogene

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
RET proto-oncogene O43519 Details

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

4. High affinity nerve growth factor receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
High affinity nerve growth factor receptor P04629 Details

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
  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
  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
  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
  5. Delbaldo C: [Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)] Therapie. 2007 Mar-Apr;62(2):87-90. Epub 2007 Jun 21. Pubmed

5. Macrophage colony-stimulating factor 1 receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Macrophage colony-stimulating factor 1 receptor P07333 Details

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
  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
  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
  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
  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

6. Platelet-derived growth factor receptor alpha

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Platelet-derived growth factor receptor alpha P16234 Details

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
  2. Borbenyi Z: [Disorders with eosinophilia, treatment of hypereosinophilic syndrome] Orv Hetil. 2005 May 1;146(18 Suppl 1):911-6. Pubmed
  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
  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
  5. Tefferi A: Modern diagnosis and treatment of primary eosinophilia. Acta Haematol. 2005;114(1):52-60. Pubmed

7. Epithelial discoidin domain-containing receptor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Epithelial discoidin domain-containing receptor 1 Q08345 Details

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
  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
  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
  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
  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

8. Tyrosine-protein kinase ABL1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Tyrosine-protein kinase ABL1 P00519 Details

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
  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
  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
  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
  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

9. Platelet-derived growth factor receptor beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Platelet-derived growth factor receptor beta P09619 Details

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
  2. Jones RL, Judson IR: The development and application of imatinib. Expert Opin Drug Saf. 2005 Mar;4(2):183-91. Pubmed
  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
  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
  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

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.
  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
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. 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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.
  2. 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
  3. 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

5. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.
  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

6. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.
  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

7. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep.

8. Prostaglandin G/H synthase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Prostaglandin G/H synthase 1 P23219 Details

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

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. FDA label

2. Alpha-1-acid glycoprotein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Alpha-1-acid glycoprotein 1 P02763 Details

References:

  1. FDA label

Transporters

1. Solute carrier family 22 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 1 O15245 Details

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. Epub 2009 Aug 27. Pubmed
  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. Epub 2010 Feb 11. Pubmed
  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. Epub 2008 Sep 13. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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. Epub 2009 Aug 27. Pubmed
  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. Epub 2010 Apr 27. Pubmed
  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
  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
  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. Epub 2009 Sep 28. Pubmed
  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. Epub 2008 Jul 31. Pubmed
  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
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters] Gan To Kagaku Ryoho. 2005 May;32(5):585-92. Pubmed
  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
  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
  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

3. Solute carrier family 22 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 2 O15244 Details

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. Epub 2009 Jun 18. Pubmed
  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

4. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

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
  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. Pubmed
  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. Epub 2009 Aug 27. Pubmed
  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. Epub 2010 Apr 27. Pubmed
  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
  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. Epub 2009 Sep 28. Pubmed
  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
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters] Gan To Kagaku Ryoho. 2005 May;32(5):585-92. Pubmed
  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
  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
  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

5. ATP-binding cassette sub-family A member 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family A member 3 Q99758 Details

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. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:23