Imatinib

Identification

Summary

Imatinib is a tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal tumors.

Brand Names
Gleevec, Glivec
Generic Name
Imatinib
DrugBank Accession Number
DB00619
Background

Imatinib is a small molecule kinase inhibitor that revolutionized the treatment of cancer, particularly chronic myeloid leukemia, in 2001.10 It was deemed a "miracle drug" due to its clinical success, as oncologist Dr. Brian noted that "complete hematologic responses were observed in 53 of 54 patients with CML treated with a daily dosage of 300 mg or more and typically occurred in the first four weeks of therapy".12. The discovery of imatinib also established a new group of therapy called "targeted therapy", since treatment can be tailored specifically to the unique cancer genetics of each patient.17

Imatinib was approved on February 1st ,2001 by the FDA and November 7th, 2001 by the EMA; however, its European approval has been withdrawn in October 2023.13,18,19

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 493.6027
Monoisotopic: 493.259008649
Chemical Formula
C29H31N7O
Synonyms
  • Imatinib
  • Imatinibum
  • α-(4-methyl-1-piperazinyl)-3'-((4-(3-pyridyl)-2-pyrimidinyl)amino)-p-toluidide
External IDs
  • CGP-57148B

Pharmacology

Indication

Imatinib is indicated for the treatment of adult and pediatric chronic myeloid leukemia with Philadelphia chromosome mutation (Ph+) in blast crisis, accelerated phase, or chronic phase after IFN-alpha therapy failure.15 Additionally, imatinib is also indicated to treat adult and pediatric Ph+ acute lymphoblastic leukemia, adult myelodysplastic/myeloproliferative diseases, adult aggressive systemic mastocytosis, adult hypereosinophilic syndrome and/or chronic eosinophilic leukemia (CEL), adult dermatofibrosarcoma protuberans, and malignant gastrointestinal stromal tumors (GIST).15

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAccelerated phase chronic myologenic leukemia••••••••••••••••••
Treatment ofAggressive systemic mastocytosis•••••••••••••••••••••••
Treatment ofChordoma••• •••••••••••
Treatment ofChronic eosinophilic leukemia (cel)•••••••••••••••••••••••
Treatment ofChronic eosinophilic leukemia (cel)•••••••••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Imatinib is a 2-phenylaminopyrimidine derivative neoplastic agent that belongs to the class of tyrosine kinase inhibitors.15 Although imatinib inhibits a number of tyrosine kinases, it is quite selective toward the BCR-ABL fusion protein that is present in various cancers.10 BCR-ABL pathway controls many downstream pathways that are heavily implicated in neoplastic growth such as the Ras/MapK pathway (cellular proliferation), Src/Pax/Fak/Rac pathway (cellular motility), and PI/PI3K/AKT/BCL-2 pathway (apoptosis pathway).7,8,9 Therefore, the BCR-ABL pathway is an attractive target for cancer treatment. Although normal cells also depend on these pathways for growth, these cells tend to have redundant tyrosine kinases to continually function in spite of ABL inhibition from imatinib.1 Cancer cells, on the other hand, can have a dependence on BCR-ABL, thus more heavily impacted by imatinib.1

Mechanism of action

Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutively active tyrosine kinase created by the Philadelphia chromosome abnormality in CML.15Although the function of normal BCR is still unclear, ABL activation is overexpressed in various tumors and is heavily implicated in cancer cells growth and survival.10,11 Imatinib inhibits the BCR-ABL protein by binding to the ATP pocket in the active site, thus preventing downstream phosphorylation of target protein.10

Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-Kit mutation.15

TargetActionsOrganism
ABreakpoint cluster region protein
inhibitor
Humans
AMast/stem cell growth factor receptor Kit
antagonist
Humans
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Humans
UHigh affinity nerve growth factor receptor
antagonist
Humans
UMacrophage colony-stimulating factor 1 receptor
antagonist
Humans
APlatelet-derived growth factor receptor alpha
antagonist
Humans
UEpithelial discoidin domain-containing receptor 1
antagonist
Humans
ATyrosine-protein kinase ABL1
inhibitor
Humans
APlatelet-derived growth factor receptor beta
antagonist
Humans
UDiscoidin domain-containing receptor 2
antagonist
Humans
Absorption

Imatinib is well absorbed after oral administration with Cmax achieved within 2-4 hours post-dose. Mean absolute bioavailability is 98%.15 Mean imatinib AUC increases proportionally with increasing doses ranging from 25 mg to 1,000 mg.15 There is no significant change in the pharmacokinetics of imatinib on repeated dosing, and accumulation is 1.5- to 2.5-fold at a steady state when Gleevec is dosed once daily.15

Volume of distribution

Population pharmacokinetics in adult CML patients estimated the steady-state volume of distribution of imatinib to be 295.0 ± 62.5 L.6At a dose of 340 mg/m2, the volume of distribution of imatinib in pediatric patients was calculated to be 167 ± 84 L.6

Protein binding

At clinically relevant concentrations of imatinib, binding to plasma proteins in in vitro experiments is approximately 95%, mostly to albumin and α1-acid glycoprotein.15

Metabolism

CYP3A4 is the major enzyme responsible for the metabolism of imatinib. 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. It shows in vitro potency similar to the parent imatinib.15

Hover over products below to view reaction partners

Route of elimination

Imatinib elimination is predominately in the feces, mostly as metabolites. Based on the recovery of compound(s) after an oral 14C-labeled dose of imatinib, approximately 81% of the dose was eliminated within 7 days, in feces (68% of dose) and urine (13% of dose).15 Unchanged imatinib accounted for 25% of the dose (5% urine, 20% feces), the remainder being metabolites.15

Half-life

Following oral administration in healthy volunteers, the elimination half-lives of imatinib and its major active metabolite, the N-desmethyl derivative (CGP74588), are approximately 18 and 40 hours, respectively.15

Clearance

Typically, clearance of imatinib in a 50-year-old patient weighing 50 kg is expected to be 8 L/h, while for a 50-year-old patient weighing 100 kg the clearance will increase to 14 L/h. The inter-patient variability of 40% in clearance does not warrant initial dose adjustment based on body weight and/or age but indicates the need for close monitoring for treatment-related toxicities.15

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

The most frequently reported adverse reactions (>30%) were edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.15

In the 2-year rat carcinogenicity study administration of imatinib at 15, 30, and 60 mg/kg/day resulted in a statistically significant reduction in the longevity of males at 60 mg/kg/day and females at greater than or equal to 30 mg/kg/day. Target organs for neoplastic changes were the kidneys (renal tubule and renal pelvis), urinary bladder, urethra, preputial and clitoral gland, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach. Neoplastic lesions were not seen at 30 mg/kg/day for the kidneys, urinary bladder, urethra, small intestine, parathyroid glands, adrenal glands, and non-glandular stomach, and 15 mg/kg/day for the preputial and clitoral gland. The papilloma/carcinoma of the preputial/clitoral gland was noted at 30 and 60 mg/kg/day, representing approximately 0.5 to 4 or 0.3 to 2.4 times the human daily exposure (based on AUC) at 400 mg/day or 800 mg/day, respectively, and 0.4 to 3.0 times the daily exposure in children (based on AUC) at 340 mg/m2. The renal tubule adenoma/carcinoma, renal pelvis transitional cell neoplasms, the urinary bladder and urethra transitional cell papillomas, the small intestine adenocarcinomas, the parathyroid glands adenomas, the benign and malignant medullary tumors of the adrenal glands and the non-glandular stomach papillomas/carcinomas were noted at 60 mg/kg/day. The relevance of these findings in the rat carcinogenicity study for humans is not known. Positive genotoxic effects were obtained for imatinib in an in vitro mammalian cell assay (Chinese hamster ovary) for clastogenicity (chromosome aberrations) in the presence of metabolic activation. Two intermediates of the manufacturing process, which are also present in the final product, are positive for mutagenesis in the Ames assay. One of these intermediates was also positive in the mouse lymphoma assay. Imatinib was not genotoxic when tested in an in vitro bacterial cell assay (Ames test), an in vitro mammalian cell assay (mouse lymphoma) and an in vivo rat micronucleus assay.15

In a study of fertility, male rats were dosed for 70 days prior to mating and female rats were dosed 14 days prior to mating and through to gestational Day 6. Testicular and epididymal weights and percent motile sperm were decreased at 60 mg/kg, approximately three-fourths the maximum clinical dose of 800 mg/day based on BSA. This was not seen at doses less than or equal to 20 mg/kg (one-fourth of the maximum human dose of 800 mg). The fertility of male and female rats was not affected.15

Fertility was not affected in the preclinical fertility and early embryonic development study although lower testes and epididymal weights, as well as a reduced number of motile sperm, were observed in the high-dose male rats. In the preclinical pre-and postnatal study in rats, fertility in the first generation offspring was also not affected by imatinib mesylate.15

It is important to consider potential toxicities suggested by animal studies, specifically, liver, kidney, and cardiac toxicity and immunosuppression. Severe liver toxicity was observed in dogs treated for 2 weeks, with elevated liver enzymes, hepatocellular necrosis, bile duct necrosis, and bile duct hyperplasia. Renal toxicity was observed in monkeys treated for 2 weeks, with focal mineralization and dilation of the renal tubules and tubular nephrosis. Increased blood urea nitrogen (BUN) and creatinine were observed in several of these animals. An increased rate of opportunistic infections was observed with chronic imatinib treatment in laboratory animal studies. In a 39-week monkey study, treatment with imatinib resulted in the worsening of normally suppressed malarial infections in these animals. Lymphopenia was observed in animals (as in humans). Additional long-term toxicities were identified in a 2-year rat study. Histopathological examination of the treated rats that died in the study revealed cardiomyopathy (both sexes), chronic progressive nephropathy (females), and preputial gland papilloma as principal causes of death or reasons for sacrifice. Non-neoplastic lesions seen in this 2-year study that were not identified in earlier preclinical studies were the cardiovascular system, pancreas, endocrine organs, and teeth. The most important changes included cardiac hypertrophy and dilatation, leading to signs of cardiac insufficiency in some animals.15

Pathways
PathwayCategory
Imatinib Inhibition of BCR-ABLDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Imatinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Imatinib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Imatinib.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Imatinib.
AbirateroneThe serum concentration of Imatinib can be increased when it is combined with Abiraterone.
Food Interactions
  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which can increase serum levels of imatinib.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of imatinib.
  • Take with a full glass of water. Taking imatinib with water may reduce gastric irritation.
  • Take with food. Food reduces gastric irritation.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Imatinib mesylate8A1O1M485B220127-57-1YLMAHDNUQAMNNX-UHFFFAOYSA-N
International/Other Brands
Celonib (Celon) / Enliven (Orion) / Imatib (Grey Inversiones) / Mesylonib (Miracalus) / Mitinab (Glenmark) / Plivatinib (Pliva) / Shantinib (Shantha)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GleevecTablet100 mg/1OralNovartis Pharmaceuticals Corporation2001-05-15Not applicableUS flag
GleevecTablet100 mg/1OralPhysicians Total Care, Inc.2005-10-072013-06-30US flag
GleevecCapsule100 mgOralNovartis2001-09-262008-09-24Canada flag
GleevecTablet100 mg/1OralAvera McKennan Hospital2015-03-012017-05-24US flag
GleevecTablet400 mg/1OralNovartis Pharmaceuticals Corporation2001-05-152017-05-31US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ach-imatinibTablet400 mgOralAccord Healthcare Inc2020-11-24Not applicableCanada flag
Ach-imatinibTablet100 mgOralAccord Healthcare Inc2020-11-24Not applicableCanada flag
Apo-imatinibTablet400 mgOralApotex Corporation2013-04-19Not applicableCanada flag
Apo-imatinibTablet100 mgOralApotex Corporation2013-04-19Not applicableCanada flag
ImatinibTablet400 mg/1OralDr.Reddy's Laboratories Inc2018-08-13Not applicableUS flag

Categories

ATC Codes
L01EA01 — Imatinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzanilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with a benzene ring. They have the general structure RNC(=O)R', where R,R'= benzene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Benzanilides
Alternative Parents
Pyridinylpyrimidines / Benzamides / Diaminotoluenes / Aniline and substituted anilines / Benzoyl derivatives / Benzylamines / Phenylmethylamines / N-methylpiperazines / Aminopyrimidines and derivatives / Aralkylamines
show 11 more
Substituents
1,4-diazinane / Amine / Amino acid or derivatives / Aminopyrimidine / Aniline or substituted anilines / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzamide / Benzanilide
show 27 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
pyrimidines, benzamides, pyridines, aromatic amine, N-methylpiperazine (CHEBI:45783)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
BKJ8M8G5HI
CAS number
152459-95-5
InChI Key
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

References

Synthesis Reference
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Peng B, Lloyd P, Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. doi: 10.2165/00003088-200544090-00001. [Article]
  7. Cilloni D, Saglio G: Molecular pathways: BCR-ABL. Clin Cancer Res. 2012 Feb 15;18(4):930-7. doi: 10.1158/1078-0432.CCR-10-1613. Epub 2011 Dec 8. [Article]
  8. Haguet H, Douxfils J, Chatelain C, Graux C, Mullier F, Dogne JM: BCR-ABL Tyrosine Kinase Inhibitors: Which Mechanism(s) May Explain the Risk of Thrombosis? TH Open. 2018 Feb 14;2(1):e68-e88. doi: 10.1055/s-0038-1624566. eCollection 2018 Jan. [Article]
  9. Bernt KM, Hunger SP: Current concepts in pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia. Front Oncol. 2014 Mar 25;4:54. doi: 10.3389/fonc.2014.00054. eCollection 2014. [Article]
  10. Iqbal N, Iqbal N: Imatinib: a breakthrough of targeted therapy in cancer. Chemother Res Pract. 2014;2014:357027. doi: 10.1155/2014/357027. Epub 2014 May 19. [Article]
  11. Greuber EK, Smith-Pearson P, Wang J, Pendergast AM: Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nat Rev Cancer. 2013 Aug;13(8):559-71. doi: 10.1038/nrc3563. Epub 2013 Jul 11. [Article]
  12. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996 May;2(5):561-6. doi: 10.1038/nm0596-561. [Article]
  13. Dagher R, Cohen M, Williams G, Rothmann M, Gobburu J, Robbie G, Rahman A, Chen G, Staten A, Griebel D, Pazdur R: Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res. 2002 Oct;8(10):3034-8. [Article]
  14. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet [Link]
  15. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet 2022 [Link]
  16. Cayman Chemical: Imatinib MSDS [Link]
  17. How Imatinib Transformed Leukemia Treatment and Cancer Research [Link]
  18. Imatinib Koanaa [Link]
  19. Imatinib Glivec [Link]
Human Metabolome Database
HMDB0014757
KEGG Drug
D01441
PubChem Compound
5291
PubChem Substance
46505055
ChemSpider
5101
BindingDB
13530
RxNav
282388
ChEBI
45783
ChEMBL
CHEMBL941
ZINC
ZINC000019632618
Therapeutic Targets Database
DNC001383
PharmGKB
PA10804
PDBe Ligand
STI
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Imatinib
PDB Entries
1iep / 1opj / 1t46 / 1xbb / 2hyy / 2oiq / 2pl0 / 3fw1 / 3gvu / 3hec
show 16 more
FDA label
Download (129 KB)
MSDS
Download (217 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentChronyc Myeloid Leukemia1
4Active Not RecruitingTreatmentGIST and CML1
4CompletedNot AvailableChronic Myeloid Leukemia (CML)1
4CompletedOtherChronic Myeloid Leukemia (CML)1
4CompletedTreatmentBreast Cancer1

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Murfreesboro Pharmaceutical Nursing Supply
  • Novartis AG
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral100 mg
TabletOral400 mg
Tablet, film coatedOral100.0 mg
TabletOral478 mg
TabletOral100.00 mg
TabletOral100 mg/1
TabletOral400 mg/1
CapsuleOral50 MG
TabletOral400.000 mg
Tablet, film coatedOral119.5 MG
Tablet, film coatedOral200 mg
Tablet, film coatedOral100.00 mg
Tablet, film coatedOral400.00 mg
Tablet, film coatedOral478 MG
Tablet, for solution; tablet, for suspensionOral100 MG
Tablet, for solution; tablet, for suspensionOral400 MG
CapsuleOral200 MG
CapsuleOral400 MG
CapsuleOral
Tablet, for suspensionOral
SolutionOral80 mg/mL
Tablet, film coatedOral
Tablet, coatedOral100 mg/1
Tablet, coatedOral400 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral400 mg/1
CapsuleOral100 MG
Tablet, film coatedOral600 MG
Capsule, coatedOral400 mg
TabletOral400.00 mg
TabletOral119.500 mg
TabletOral100.000 mg
Tablet, film coatedOral119.47 Mg
Tablet, film coatedOral477.88 MG
Tablet, coatedOral100 mg
Tablet, coatedOral400 mg
Capsule, coatedOral100 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral400 mg
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)Region
CA2093203No2002-11-262013-04-01Canada flag
USRE43932Yes2013-01-152019-07-16US flag
US7544799Yes2009-06-092019-07-16US flag
US6894051Yes2005-05-172019-11-23US flag
US6958335Yes2005-10-252022-06-19US flag
US5521184Yes1996-05-282015-07-04US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)226 °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)12.69Chemaxon
pKa (Strongest Basic)7.84Chemaxon
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
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-01bd-9863300000-bf69c843c9ad9179bcdb
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0006-0036900000-e06abe669a9b1b57e2c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0000900000-3974d719909aa7a75039
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0006-0000900000-dd386ae17930da36c11f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0f6x-0159500000-576f293e026deaa1ec7f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0ik9-0495000000-06102c4afd3c2e88cf87
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-03ka-0971000000-b487f693e17cba198e37
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-05fs-0930000000-9319811c561fd5cc8f2f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0159-4910000000-25480eb9451aee843c26
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9000000000-0638bee21655c0e0ca00
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-9000000000-76f9b62b017fe8241e67
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0000900000-9825e12c65f9bf36d72f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-1029200000-acd76280414e767f0280
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-2269000000-f55e5c707c9de5ba2d0f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00ba-3494000000-19e7d8361f050ec8b637
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00ba-3693000000-c1e011113081e3341bba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0596-5981000000-a0f689cd067d45644bcd
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f9f-5930000000-71f05e812cf29e11cc69
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00ku-5910000000-3f91ea6a6f7402767a78
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-029i-7900000000-507c771376ea4b799b6d
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0191000000-fb24a3158c9475186c82
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0006-0036900000-e06abe669a9b1b57e2c3
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-3379600000-f122458b106bcf2c8b8e
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0010900000-c01aa625c5ea646a6b5c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-0000900000-84708e1ff86709814513
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0006-0002900000-fc1a0c4dfe8ce711662e
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000f-0001900000-be62e6b57a0e37658538
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kf-0933800000-1af91d3c275b32f25724
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00kv-4931800000-bb2599613a18f97d37d9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-264.4177818
predicted
DarkChem Lite v0.1.0
[M-H]-264.2338818
predicted
DarkChem Lite v0.1.0
[M-H]-215.90251
predicted
DeepCCS 1.0 (2019)
[M+H]+264.6296818
predicted
DarkChem Lite v0.1.0
[M+H]+264.6094818
predicted
DarkChem Lite v0.1.0
[M+H]+218.29808
predicted
DeepCCS 1.0 (2019)
[M+Na]+263.8360818
predicted
DarkChem Lite v0.1.0
[M+Na]+264.4182818
predicted
DarkChem Lite v0.1.0
[M+Na]+224.21059
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Rho guanyl-nucleotide exchange factor activity
Specific Function
GTPase-activating protein for RAC1 and CDC42. Promotes the exchange of RAC or CDC42-bound GDP by GTP, thereby activating them. Displays serine/threonine kinase activity.
Gene Name
BCR
Uniprot ID
P11274
Uniprot Name
Breakpoint cluster region protein
Molecular Weight
142818.07 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. [Article]
  2. Waller CF: Imatinib mesylate. Recent Results Cancer Res. 2010;184:3-20. doi: 10.1007/978-3-642-01222-8_1. [Article]
  3. Croom KF, Perry CM: Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs. 2003;63(5):513-22; discussion 523-4. [Article]
  4. Reddy EP, Aggarwal AK: The ins and outs of bcr-abl inhibition. Genes Cancer. 2012 May;3(5-6):447-54. doi: 10.1177/1947601912462126. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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 main...
Gene Name
KIT
Uniprot ID
P10721
Uniprot Name
Mast/stem cell growth factor receptor Kit
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 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. [Article]
Kind
Protein
Organism
Humans
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 sympatheti...
Gene Name
NTRK1
Uniprot ID
P04629
Uniprot Name
High affinity nerve growth factor receptor
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  5. Delbaldo C: [Pharmacokinetic-pharmacodynamics relationships of imatinib (Glivec)]. Therapie. 2007 Mar-Apr;62(2):87-90. Epub 2007 Jun 21. [Article]
Kind
Protein
Organism
Humans
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 ...
Gene Name
CSF1R
Uniprot ID
P07333
Uniprot Name
Macrophage colony-stimulating factor 1 receptor
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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 chem...
Gene Name
PDGFRA
Uniprot ID
P16234
Uniprot Name
Platelet-derived growth factor receptor alpha
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. [Article]
  2. Borbenyi Z: [Disorders with eosinophilia, treatment of hypereosinophilic syndrome]. Orv Hetil. 2005 May 1;146(18 Suppl 1):911-6. [Article]
  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. [Article]
  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. [Article]
  5. Tefferi A: Modern diagnosis and treatment of primary eosinophilia. Acta Haematol. 2005;114(1):52-60. [Article]
Kind
Protein
Organism
Humans
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, dif...
Gene Name
DDR1
Uniprot ID
Q08345
Uniprot Name
Epithelial discoidin domain-containing receptor 1
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Day E, Waters B, Spiegel K, Alnadaf T, Manley PW, Buchdunger E, Walker C, Jarai G: Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol. 2008 Dec 3;599(1-3):44-53. doi: 10.1016/j.ejphar.2008.10.014. Epub 2008 Oct 11. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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 a...
Gene Name
ABL1
Uniprot ID
P00519
Uniprot Name
Tyrosine-protein kinase ABL1
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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...
Gene Name
PDGFRB
Uniprot ID
P09619
Uniprot Name
Platelet-derived growth factor receptor beta
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. [Article]
  2. Jones RL, Judson IR: The development and application of imatinib. Expert Opin Drug Saf. 2005 Mar;4(2):183-91. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
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 differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Req...
Gene Name
DDR2
Uniprot ID
Q16832
Uniprot Name
Discoidin domain-containing receptor 2
Molecular Weight
96735.44 Da
References
  1. Day E, Waters B, Spiegel K, Alnadaf T, Manley PW, Buchdunger E, Walker C, Jarai G: Inhibition of collagen-induced discoidin domain receptor 1 and 2 activation by imatinib, nilotinib and dasatinib. Eur J Pharmacol. 2008 Dec 3;599(1-3):44-53. doi: 10.1016/j.ejphar.2008.10.014. Epub 2008 Oct 11. [Article]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Koudriakova T, Iatsimirskaia E, Utkin I, Gangl E, Vouros P, Storozhuk E, Orza D, Marinina J, Gerber N: Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos. 1998 Jun;26(6):552-61. [Article]
  2. Filppula AM, Laitila J, Neuvonen PJ, Backman JT: Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98. doi: 10.1111/j.1476-5381.2011.01732.x. [Article]
  3. Peng B, Lloyd P, Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. doi: 10.2165/00003088-200544090-00001. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. GLEEVEC (imatinib mesylate) FDA Label [Link]
  6. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  7. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
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. [Article]
  2. Peng B, Lloyd P, Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. doi: 10.2165/00003088-200544090-00001. [Article]
  3. Adehin A, Adeagbo BA, Kennedy MA, Bolaji OO, Olugbade TA, Bolarinwa RA, Durosinmi MA: Inter-individual variation in imatinib disposition: any role for prevalent variants of CYP1A2, CYP2C8, CYP2C9, and CYP3A5 in Nigerian CML patients? Leuk Lymphoma. 2019 Jan;60(1):216-221. doi: 10.1080/10428194.2018.1466291. Epub 2018 May 9. [Article]
  4. Flockhart Table of Drug Interactions [Link]
  5. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
Curator comments
Although CYP3A7 was thought to mostly be involved in the metabolism of imatinib in pediatric patients, it was recently found that a subset of adult patients also have a significant CYP3A7 activity. [A249160]
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Adiwidjaja J, Boddy AV, McLachlan AJ: Implementation of a Physiologically Based Pharmacokinetic Modeling Approach to Guide Optimal Dosing Regimens for Imatinib and Potential Drug Interactions in Paediatrics. Front Pharmacol. 2020 Jan 30;10:1672. doi: 10.3389/fphar.2019.01672. eCollection 2019. [Article]
  2. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
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 un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
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. [Article]
  2. van Erp N, Gelderblom H, van Glabbeke M, Van Oosterom A, Verweij J, Guchelaar HJ, Debiec-Rychter M, Peng B, Blay JY, Judson I: Effect of cigarette smoking on imatinib in patients in the soft tissue and bone sarcoma group of the EORTC. Clin Cancer Res. 2008 Dec 15;14(24):8308-13. doi: 10.1158/1078-0432.CCR-08-1303. [Article]
  3. Liu XY, Xu T, Li WS, Luo J, Geng PW, Wang L, Xia MM, Chen MC, Yu L, Hu GX: The effect of apigenin on pharmacokinetics of imatinib and its metabolite N-desmethyl imatinib in rats. Biomed Res Int. 2013;2013:789184. doi: 10.1155/2013/789184. Epub 2013 Nov 28. [Article]
  4. Imatinib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Recoche I, Rousseau V, Bourrel R, Lapeyre-Mestre M, Chebane L, Despas F, Montastruc JL, Bondon-Guitton E: Drug-drug interactions with imatinib: An observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076. doi: 10.1097/MD.0000000000005076. [Article]
  2. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]

Carriers

Details
1. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
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 colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Peng B, Lloyd P, Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. doi: 10.2165/00003088-200544090-00001. [Article]
  2. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet 2022 [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
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...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Peng B, Lloyd P, Schran H: Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44(9):879-94. doi: 10.2165/00003088-200544090-00001. [Article]
  2. FDA Approved Drug Products: Gleevec (Imatinib) Oral Tablet 2022 [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
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-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. 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. [Article]
  2. 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. [Article]
  3. Watkins DB, Hughes TP, White DL: OCT1 and imatinib transport in CML: is it clinically relevant? Leukemia. 2015 Oct;29(10):1960-9. doi: 10.1038/leu.2015.170. Epub 2015 Jul 9. [Article]
Details
2. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. 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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters]. Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
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 fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  8. Oka M, Fukuda M, Soda H: [Anticancer drugs and ABC transporters]. Gan To Kagaku Ryoho. 2005 May;32(5):585-92. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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
Uniprot Name
ATP-binding cassette sub-family A member 3
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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. Au A, Baba AA, Azlan H, Norsa'adah B, Ankathil R: Clinical impact of ABCC1 and ABCC2 genotypes and haplotypes in mediating imatinib resistance among chronic myeloid leukaemia patients. J Clin Pharm Ther. 2014 Dec;39(6):685-90. doi: 10.1111/jcpt.12197. Epub 2014 Jul 24. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Hu S, Franke RM, Filipski KK, Hu C, Orwick SJ, de Bruijn EA, Burger H, Baker SD, Sparreboom A: Interaction of imatinib with human organic ion carriers. Clin Cancer Res. 2008 May 15;14(10):3141-8. doi: 10.1158/1078-0432.CCR-07-4913. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Hu S, Franke RM, Filipski KK, Hu C, Orwick SJ, de Bruijn EA, Burger H, Baker SD, Sparreboom A: Interaction of imatinib with human organic ion carriers. Clin Cancer Res. 2008 May 15;14(10):3141-8. doi: 10.1158/1078-0432.CCR-07-4913. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Hu S, Franke RM, Filipski KK, Hu C, Orwick SJ, de Bruijn EA, Burger H, Baker SD, Sparreboom A: Interaction of imatinib with human organic ion carriers. Clin Cancer Res. 2008 May 15;14(10):3141-8. doi: 10.1158/1078-0432.CCR-07-4913. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Hu S, Franke RM, Filipski KK, Hu C, Orwick SJ, de Bruijn EA, Burger H, Baker SD, Sparreboom A: Interaction of imatinib with human organic ion carriers. Clin Cancer Res. 2008 May 15;14(10):3141-8. doi: 10.1158/1078-0432.CCR-07-4913. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48