You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameDasatinib
Accession NumberDB01254
TypeSmall Molecule
GroupsApproved, Investigational
Description

Dasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML). The main targets of Dasatinib, are BCRABL, SRC, Ephrins and GFR.

Structure
Thumb
Synonyms
SynonymLanguageCode
Anh. dasatinibNot AvailableNot Available
Anhydrous dasatinibNot AvailableNot Available
BMS dasatinibNot AvailableNot Available
BMS-354825Not AvailableNot Available
DasatinibNot AvailableNot Available
Dasatinib (anh.)Not AvailableNot Available
DasatinibumNot AvailableNot Available
N-(2-CHLORO-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamideNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
SprycelNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number302962-49-8
WeightAverage: 488.006
Monoisotopic: 487.155721508
Chemical FormulaC22H26ClN7O2S
InChI KeyZBNZXTGUTAYRHI-UHFFFAOYSA-N
InChI
InChI=1S/C22H26ClN7O2S/c1-14-4-3-5-16(23)20(14)28-21(32)17-13-24-22(33-17)27-18-12-19(26-15(2)25-18)30-8-6-29(7-9-30)10-11-31/h3-5,12-13,31H,6-11H2,1-2H3,(H,28,32)(H,24,25,26,27)
IUPAC Name
N-(2-chloro-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamide
SMILES
CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassAnilides
Direct parentAnilides
Alternative parentsThiazolecarboxamides; Toluenes; Aminopyrimidines and Derivatives; Chlorobenzenes; 2,5-disubstituted Thiazoles; Diazinanes; Aryl Chlorides; Aminothiazoles; Piperazines; Tertiary Amines; Secondary Carboxylic Acid Amides; Primary Alcohols; Carboxylic Acids; Enolates; Secondary Amines; Polyamines; Organochlorides
Substituentsthiazolecarboxylic acid or derivative; thiazolecarboxamide; 2,5-disubstituted 1,3-thiazole; aminopyrimidine; toluene; chlorobenzene; aryl halide; piperazine; aryl chloride; 1,3-thiazolamine; pyrimidine; 1,4-diazinane; thiazole; azole; secondary carboxylic acid amide; tertiary amine; carboxamide group; polyamine; primary alcohol; enolate; carboxylic acid derivative; carboxylic acid; secondary amine; organohalogen; organochloride; amine; organonitrogen compound; alcohol
Classification descriptionThis compound belongs to the anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Pharmacology
IndicationFor the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy.
PharmacodynamicsDasatinib is an oral dual BCR/ABL and Src family tyrosine kinase inhibitor
Mechanism of actionDasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase. In vitro, dasatinib was active in leukemic cell lines representing variants of imatinib mesylate sensitive and resistant disease. Dasatinib inhibited the growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL. Under the conditions of the assays, dasatinib was able to overcome imatinib resistance resulting from BCR-ABL kinase domain mutations, activation of alternate signaling pathways involving the SRC family kinases (LYN, HCK), and multi-drug resistance gene overexpression.
AbsorptionNot Available
Volume of distribution
  • 2505 L
Protein binding96%
Metabolism

Dasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4

Route of eliminationDasatinib is extensively metabolized in humans, primarily by the cytochrome P450 enzyme 3A4. Elimination is primarily via the feces.
Half lifeThe overall mean terminal half-life of dasatinib is 3-5 hours.
ClearanceNot Available
ToxicityAcute overdose in animals was associated with cardiotoxicity.
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 + 0.9852
Blood Brain Barrier - 0.507
Caco-2 permeable - 0.5638
P-glycoprotein substrate Substrate 0.6562
P-glycoprotein inhibitor I Inhibitor 0.5371
P-glycoprotein inhibitor II Inhibitor 0.5425
Renal organic cation transporter Non-inhibitor 0.7288
CYP450 2C9 substrate Non-substrate 0.7061
CYP450 2D6 substrate Non-substrate 0.8152
CYP450 3A4 substrate Substrate 0.5704
CYP450 1A2 substrate Non-inhibitor 0.5612
CYP450 2C9 substrate Inhibitor 0.8008
CYP450 2D6 substrate Non-inhibitor 0.8358
CYP450 2C19 substrate Inhibitor 0.574
CYP450 3A4 substrate Inhibitor 0.7295
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.8343
Ames test Non AMES toxic 0.7185
Carcinogenicity Non-carcinogens 0.7308
Biodegradation Not ready biodegradable 0.9863
Rat acute toxicity 2.4772 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8538
hERG inhibition (predictor II) Inhibitor 0.718
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb co
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Sprycel 100 mg tablet278.24USDtablet
Sprycel 50 mg tablet139.12USDtablet
Sprycel 70 mg tablet139.12USDtablet
Sprycel 20 mg tablet69.56USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States74917252005-10-132025-10-13
United States71258752000-04-132020-04-13
Canada23669322009-08-252020-04-12
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point280-286 °CNot Available
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0128ALOGPS
logP2.77ALOGPS
logP3.82ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)8.49ChemAxon
pKa (Strongest Basic)7.22ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area106.51 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity133.08 m3·mol-1ChemAxon
Polarizability51.58 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceUS6596746
General Reference
  1. Das J, Chen P, Norris D, Padmanabha R, Lin J, Moquin RV, Shen Z, Cook LS, Doweyko AM, Pitt S, Pang S, Shen DR, Fang Q, de Fex HF, McIntyre KW, Shuster DJ, Gillooly KM, Behnia K, Schieven GL, Wityak J, Barrish JC: 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. J Med Chem. 2006 Nov 16;49(23):6819-32. Pubmed
  2. Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, Cortes J, O’Brien S, Nicaise C, Bleickardt E, Blackwood-Chirchir MA, Iyer V, Chen TT, Huang F, Decillis AP, Sawyers CL: Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006 Jun 15;354(24):2531-41. Pubmed
External Links
ResourceLink
KEGG DrugD03658
PubChem Compound3062316
PubChem Substance46505143
ChemSpider2323020
BindingDB13216
ChEBI49375
ChEMBLCHEMBL1421
Therapeutic Targets DatabaseDAP000004
PharmGKBPA162372878
RxListhttp://www.rxlist.com/cgi/generic/sprycel.htm
Drugs.comhttp://www.drugs.com/cdi/dasatinib.html
WikipediaDasatinib
ATC CodesL01XE06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(237 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
EptifibatideMonitor therapy due to enhanced anticoagulant effect.
EtravirineDasatinib, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to avoid this combination if possible. If concurrent therapy cannot be avoided it is recommended to increase the dose of dasitinib and monitor for efficacy and toxicity.
OmeprazoleOmeprazole may decrease the serum level of dasatinib.
PantoprazolePantoprazole may decrease the serum level of dasatinib.
PhenobarbitalPhenobarbital may decrease the serum level and efficacy of dasatinib.
PhenytoinPhenytoin may decrease the serum level and efficacy of dasatinib.
RabeprazoleRabeprazole may decrease the serum level of dasatinib.
RanitidineRanitidine may decrease the serum level of dasatinib.
RifampicinRifampin may decrease the serum level and efficacy of dasatinib.
TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
TelithromycinTelithromycin may reduce clearance of Dasatinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Dasatinib if Telithromycin is initiated, discontinued or dose changed.
ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
TrimipramineAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
VoriconazoleAdditive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of dasatinib by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of dasatinib if voriconazole is initiated, discontinued or dose changed.
VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food InteractionsNot Available

Targets

1. Tyrosine-protein kinase ABL1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: multitarget

Components

Name UniProt ID Details
Tyrosine-protein kinase ABL1 P00519 Details

References:

  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  2. Piccaluga PP, Paolini S, Martinelli G: Tyrosine kinase inhibitors for the treatment of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Cancer. 2007 Sep 15;110(6):1178-86. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Proto-oncogene tyrosine-protein kinase Src

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: multitarget

Components

Name UniProt ID Details
Proto-oncogene tyrosine-protein kinase Src P12931 Details

References:

  1. Kamath AV, Wang J, Lee FY, Marathe PH: Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL. Cancer Chemother Pharmacol. 2007 Apr 11;. Pubmed
  2. Serrels A, Macpherson IR, Evans TR, Lee FY, Clark EA, Sansom OJ, Ashton GH, Frame MC, Brunton VG: Identification of potential biomarkers for measuring inhibition of Src kinase activity in colon cancer cells following treatment with dasatinib. Mol Cancer Ther. 2006 Dec;5(12):3014-22. Epub 2006 Dec 5. Pubmed
  3. Quintas-Cardama A, Kantarjian H, Cortes J: Targeting ABL and SRC kinases in chronic myeloid leukemia: experience with dasatinib. Future Oncol. 2006 Dec;2(6):655-65. Pubmed
  4. Schittenhelm MM, Shiraga S, Schroeder A, Corbin AS, Griffith D, Lee FY, Bokemeyer C, Deininger MW, Druker BJ, Heinrich MC: Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 2006 Jan 1;66(1):473-81. Pubmed
  5. Nam S, Kim D, Cheng JQ, Zhang S, Lee JH, Buettner R, Mirosevich J, Lee FY, Jove R: Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer Res. 2005 Oct 15;65(20):9185-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

3. Ephrin type-A receptor 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Ephrin type-A receptor 2 P29317 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed

4. Tyrosine-protein kinase Lck

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: multitarget

Components

Name UniProt ID Details
Tyrosine-protein kinase Lck P06239 Details

References:

  1. Das J, Chen P, Norris D, Padmanabha R, Lin J, Moquin RV, Shen Z, Cook LS, Doweyko AM, Pitt S, Pang S, Shen DR, Fang Q, de Fex HF, McIntyre KW, Shuster DJ, Gillooly KM, Behnia K, Schieven GL, Wityak J, Barrish JC: 2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1- piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (dasatinib, BMS-354825) as a potent pan-Src kinase inhibitor. J Med Chem. 2006 Nov 16;49(23):6819-32. Pubmed
  2. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

5. Tyrosine-protein kinase Yes

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Tyrosine-protein kinase Yes P07947 Details

References:

  1. Trevino JG, Summy JM, Lesslie DP, Parikh NU, Hong DS, Lee FY, Donato NJ, Abbruzzese JL, Baker CH, Gallick GE: Inhibition of SRC expression and activity inhibits tumor progression and metastasis of human pancreatic adenocarcinoma cells in an orthotopic nude mouse model. Am J Pathol. 2006 Mar;168(3):962-72. Pubmed
  2. Margutti S, Laufer SA: Are MAP Kinases Drug Targets? Yes, but Difficult Ones. ChemMedChem. 2007 Aug 13;2(8):1116-1140. Pubmed
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed

6. Mast/stem cell growth factor receptor Kit

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

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

References:

  1. Schittenhelm MM, Shiraga S, Schroeder A, Corbin AS, Griffith D, Lee FY, Bokemeyer C, Deininger MW, Druker BJ, Heinrich MC: Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res. 2006 Jan 1;66(1):473-81. Pubmed
  2. Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C: Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91. Epub 2006 Jan 24. Pubmed
  3. Dizdar O, Dede DS, Bulut N, Altundag K: Dasatinib may also inhibit c-Kit in triple negative breast cancer cell lines. Breast Cancer Res Treat. 2007 Mar 10;. Pubmed

7. 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. Zhang Z, Meier KE: New assignments for multitasking signal transduction inhibitors. Mol Pharmacol. 2006 May;69(5):1510-2. Epub 2006 Feb 23. Pubmed
  2. Chen Z, Lee FY, Bhalla KN, Wu J: Potent inhibition of platelet-derived growth factor-induced responses in vascular smooth muscle cells by BMS-354825 (dasatinib). Mol Pharmacol. 2006 May;69(5):1527-33. Epub 2006 Jan 25. Pubmed
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed

8. Signal transducer and activator of transcription 5B

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Signal transducer and activator of transcription 5B P51692 Details

References:

  1. Fiskus W, Pranpat M, Balasis M, Bali P, Estrella V, Kumaraswamy S, Rao R, Rocha K, Herger B, Lee F, Richon V, Bhalla K: Cotreatment with vorinostat (suberoylanilide hydroxamic acid) enhances activity of dasatinib (BMS-354825) against imatinib mesylate-sensitive or imatinib mesylate-resistant chronic myelogenous leukemia cells. Clin Cancer Res. 2006 Oct 1;12(19):5869-78. Pubmed
  2. Nam S, Williams A, Vultur A, List A, Bhalla K, Smith D, Lee FY, Jove R: Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells. Mol Cancer Ther. 2007 Apr;6(4):1400-5. Pubmed

9. Abelson tyrosine-protein kinase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: multitarget

Components

Name UniProt ID Details
Abelson tyrosine-protein kinase 2 P42684 Details

References:

  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  2. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

10. Tyrosine-protein kinase Fyn

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: multitarget

Components

Name UniProt ID Details
Tyrosine-protein kinase Fyn P06241 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed# van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

2. Cytochrome P450 1A1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A1 P04798 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

3. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

4. Cytochrome P450 1B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1B1 Q16678 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

5. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. Epub 2009 Sep 5. Pubmed
  2. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

6. Dimethylaniline monooxygenase [N-oxide-forming] 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Dimethylaniline monooxygenase [N-oxide-forming] 3 P31513 Details

References:

  1. Wang L, Christopher LJ, Cui D, Li W, Iyer R, Humphreys WG, Zhang D: Identification of the human enzymes involved in the oxidative metabolism of dasatinib: an effective approach for determining metabolite formation kinetics. Drug Metab Dispos. 2008 Sep;36(9):1828-39. Epub 2008 Jun 12. Pubmed

Transporters

1. 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. 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
  2. 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
  3. 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

2. 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. 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
  2. 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

Comments
comments powered by Disqus
Drug created on May 08, 2007 18:32 / Updated on July 14, 2014 13:31