Hmdb loader
Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:52 UTC
Update Date2022-03-07 02:51:58 UTC
HMDB IDHMDB0015384
Secondary Accession Numbers
  • HMDB15384
Metabolite Identification
Common NameDasatinib
DescriptionDasatinib is only found in individuals that have used or taken this drug. It 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.Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFR&beta. 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.
Structure
Data?1582753290
Synonyms
ValueSource
Anh. dasatinibChEBI
Anhydrous dasatinibChEBI
BMS DasatinibChEBI
BMS-354825ChEBI
Dasatinib (anh.)ChEBI
DasatinibumChEBI
N-(2-CHLORO-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamideChEBI
(18F)-N-(2-Chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamideHMDB
N-(2-Chloro-6-methylphenyl)-2-(6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamideHMDB
SprycelHMDB
Chemical FormulaC22H26ClN7O2S
Average Molecular Weight488.006
Monoisotopic Molecular Weight487.155721508
IUPAC NameN-(2-chloro-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamide
Traditional Namedasatinib
CAS Registry Number302962-49-8
SMILES
CC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC1
InChI Identifier
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)
InChI KeyZBNZXTGUTAYRHI-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • Amphetamine or derivatives
  • Phenylpropane
  • Monocyclic benzene moiety
  • Fatty amide
  • Fatty acyl
  • Benzenoid
  • N-acyl-amine
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Primary amine
  • Primary aliphatic amine
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Ontology
Physiological effectNot Available
Disposition
Process
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point280 - 286 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.013 g/LNot Available
LogP1.8Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity133.08 m³·mol⁻¹ChemAxon
Polarizability51.58 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+201.83930932474
DeepCCS[M-H]-199.48130932474
DeepCCS[M-2H]-232.97530932474
DeepCCS[M+Na]+208.10130932474
AllCCS[M+H]+211.932859911
AllCCS[M+H-H2O]+210.132859911
AllCCS[M+NH4]+213.532859911
AllCCS[M+Na]+214.032859911
AllCCS[M-H]-203.132859911
AllCCS[M+Na-2H]-203.832859911
AllCCS[M+HCOO]-204.832859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
DasatinibCC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC15206.7Standard polar33892256
DasatinibCC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC14189.0Standard non polar33892256
DasatinibCC1=NC(NC2=NC=C(S2)C(=O)NC2=C(C)C=CC=C2Cl)=CC(=N1)N1CCN(CCO)CC14719.5Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Dasatinib,1TMS,isomer #1CC1=NC(NC2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)=CC(N2CCN(CCO[Si](C)(C)C)CC2)=N14517.2Semi standard non polar33892256
Dasatinib,1TMS,isomer #2CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C)=N14255.2Semi standard non polar33892256
Dasatinib,1TMS,isomer #3CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)=CC(N2CCN(CCO)CC2)=N14251.3Semi standard non polar33892256
Dasatinib,2TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C)=N14227.8Semi standard non polar33892256
Dasatinib,2TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C)=N13773.6Standard non polar33892256
Dasatinib,2TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C)=N15843.0Standard polar33892256
Dasatinib,2TMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C)CC2)=N14195.4Semi standard non polar33892256
Dasatinib,2TMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C)CC2)=N13755.0Standard non polar33892256
Dasatinib,2TMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C)CC2)=N16089.6Standard polar33892256
Dasatinib,2TMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N13984.0Semi standard non polar33892256
Dasatinib,2TMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N13746.2Standard non polar33892256
Dasatinib,2TMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N15683.9Standard polar33892256
Dasatinib,3TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N13999.1Semi standard non polar33892256
Dasatinib,3TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N13677.1Standard non polar33892256
Dasatinib,3TMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C)S2)[Si](C)(C)C)=N15280.9Standard polar33892256
Dasatinib,1TBDMS,isomer #1CC1=NC(NC2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)=CC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=N14699.9Semi standard non polar33892256
Dasatinib,1TBDMS,isomer #2CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C(C)(C)C)=N14437.8Semi standard non polar33892256
Dasatinib,1TBDMS,isomer #3CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)=CC(N2CCN(CCO)CC2)=N14441.3Semi standard non polar33892256
Dasatinib,2TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C(C)(C)C)=N14573.0Semi standard non polar33892256
Dasatinib,2TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C(C)(C)C)=N14120.3Standard non polar33892256
Dasatinib,2TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)[Si](C)(C)C(C)(C)C)=N15734.7Standard polar33892256
Dasatinib,2TBDMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=N14534.7Semi standard non polar33892256
Dasatinib,2TBDMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=N14139.8Standard non polar33892256
Dasatinib,2TBDMS,isomer #2CC1=NC(NC2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)=CC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=N15998.6Standard polar33892256
Dasatinib,2TBDMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N14334.9Semi standard non polar33892256
Dasatinib,2TBDMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N14120.9Standard non polar33892256
Dasatinib,2TBDMS,isomer #3CC1=NC(N2CCN(CCO)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N15559.2Standard polar33892256
Dasatinib,3TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N14502.8Semi standard non polar33892256
Dasatinib,3TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N14220.6Standard non polar33892256
Dasatinib,3TBDMS,isomer #1CC1=NC(N2CCN(CCO[Si](C)(C)C(C)(C)C)CC2)=CC(N(C2=NC=C(C(=O)N(C3=C(C)C=CC=C3Cl)[Si](C)(C)C(C)(C)C)S2)[Si](C)(C)C(C)(C)C)=N15260.7Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Dasatinib GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4j-3104900000-19c063b36c545a5eb85a2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Dasatinib GC-MS (1 TMS) - 70eV, Positivesplash10-00r7-3101490000-d274cb5f2cc0589526f62017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Dasatinib GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Dasatinib , positive-QTOFsplash10-000m-0390000000-8a413cb9e53d14cbe10a2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Dasatinib , positive-QTOFsplash10-000i-0011900000-4dac51b915117532ebe02017-09-14HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 10V, Positive-QTOFsplash10-000l-0521900000-f036db5f090dc721c0612016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 20V, Positive-QTOFsplash10-0006-0945000000-1344a7f6fa72fda9679c2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 40V, Positive-QTOFsplash10-0006-1941000000-7dd50ec0e4437edbdddb2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 10V, Negative-QTOFsplash10-06ri-0293600000-003749b25fb59315664f2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 20V, Negative-QTOFsplash10-066v-1292100000-f90b69c609d80d3f92a82016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 40V, Negative-QTOFsplash10-0a4i-3390000000-0e74e360d8dc98f4adc82016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 10V, Positive-QTOFsplash10-000i-0000900000-e70e9316e0f943fd209d2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 20V, Positive-QTOFsplash10-000i-0001900000-009c64fdb2ae58cfd0fb2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 40V, Positive-QTOFsplash10-0f72-7395800000-2de6701f9f023ff4fc042021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 10V, Negative-QTOFsplash10-000i-0000900000-25ba0df4df3ee5cf8e032021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 20V, Negative-QTOFsplash10-0fs9-4112900000-d8d24063d0379ec5b3372021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Dasatinib 40V, Negative-QTOFsplash10-001i-4192000000-f29c2b38b827f08243f62021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01254 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01254 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01254
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2323020
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDasatinib
METLIN IDNot Available
PubChem Compound3062316
PDB IDNot Available
ChEBI ID49375
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General 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:17154512 ]
  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:16775234 ]

Only showing the first 10 proteins. There are 17 proteins in total.

Enzymes

General function:
Involved in flavin-containing monooxygenase activity
Specific function:
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds.
Gene Name:
FMO3
Uniprot ID:
P31513
Molecular weight:
60032.975
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. doi: 10.1124/dmd.107.020255. Epub 2008 Jun 12. [PubMed:18556438 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
  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. doi: 10.1124/dmd.107.020255. Epub 2008 Jun 12. [PubMed:18556438 ]
General function:
Involved in protein kinase activity
Specific function:
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Gene Name:
SRC
Uniprot ID:
P12931
Molecular weight:
59834.3
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. 2008 Mar;61(3):365-76. Epub 2007 Apr 11. [PubMed:17429625 ]
  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:17148760 ]
  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:17155893 ]
  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:16397263 ]
  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:16230377 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in protein kinase activity
Specific function:
Promotes infectivity of Neisseria gonorrhoeae in epithelial cells by phosphorylating MCP/CD46
Gene Name:
YES1
Uniprot ID:
P07947
Molecular weight:
60800.8
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:16507911 ]
  2. Margutti S, Laufer SA: Are MAP kinases drug targets? Yes, but difficult ones. ChemMedChem. 2007 Aug;2(8):1116-40. [PubMed:17541990 ]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]
General function:
Involved in ephrin receptor activity
Specific function:
Receptor for members of the ephrin-A family. Binds to ephrin-A1, -A3, -A4 and -A5. Plays an important role in angiogenesis and tumor neovascularization. The recruitement of VAV2, VAV3 and PI3-kinase p85 subunit by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly. Induces apoptosis in a TP53/p53-independent, caspase-8-dependent manner
Gene Name:
EPHA2
Uniprot ID:
P29317
Molecular weight:
108265.6
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]
General function:
Involved in protein kinase activity
Specific function:
Implicated in the control of cell growth. Plays a role in the regulation of intracellular calcium levels, with isoform 2 showing the greater ability to mobilize cytoplasmic calcium in comparison to isoform 1. Required in brain development and mature brain function with important roles in the regulation of axon growth, axon guidance, and neurite extension. Blocks axon outgrowth and attraction induced by NTN1 by phosphorylating its receptor DDC
Gene Name:
FYN
Uniprot ID:
P06241
Molecular weight:
60761.5
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in non-membrane spanning protein tyrosine kinase activity
Specific function:
Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks
Gene Name:
ABL2
Uniprot ID:
P42684
Molecular weight:
128341.9
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:17016423 ]
  2. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in protein kinase activity
Specific function:
Tyrosine kinase that plays an essential role for the selection and maturation of developing T-cell in the thymus and in mature T-cell function. Is constitutively associated with the cytoplasmic portions of the CD4 and CD8 surface receptors and plays a key role in T-cell antigen receptor(TCR)-linked signal transduction pathways. Association of the TCR with a peptide antigen-bound MHC complex facilitates the interaction of CD4 and CD8 with MHC class II and class I molecules, respectively, and thereby recruits the associated LCK to the vicinity of the TCR/CD3 complex. LCK then phosphorylates tyrosines residues within the immunoreceptor tyrosines-based activation motifs (ITAMs) in the cytoplasmic tails of the TCRgamma chains and CD3 subunits, initiating the TCR/CD3 signaling pathway. In addition, contributes to signaling by other receptor molecules. Associates directly with the cytoplasmic tail of CD2, and upon engagement of the CD2 molecule, LCK undergoes hyperphosphorylation and activation. Also plays a role in the IL2 receptor-linked signaling pathway that controls T-cell proliferative response. Binding of IL2 to its receptor results in increased activity of LCK. Is expressed at all stages of thymocyte development and is required for the regulation of maturation events that are governed by both pre-TCR and mature alpha beta TCR
Gene Name:
LCK
Uniprot ID:
P06239
Molecular weight:
58000.1
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:17154512 ]
  2. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in non-membrane spanning protein tyrosine kinase activity
Specific function:
Protein kinase that regulates key processes linked to cell growth and survival. Regulates cytoskeleton remodeling during cell differentiation, cell division and cell adhesion. Localizes to dynamic actin structures, and phosphorylates CRK and CRKL, DOK1, and other proteins controlling cytoskeleton dynamics. Regulates DNA repair potentially by activating the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks
Gene Name:
ABL1
Uniprot ID:
P00519
Molecular weight:
122871.4
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:17016423 ]
  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:17701954 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in protein kinase activity
Specific function:
Receptor that binds specifically to PDGFB and PDGFD and has a tyrosine-protein kinase activity. Phosphorylates Tyr residues at the C-terminus of PTPN11 creating a binding site for the SH2 domain of GRB2
Gene Name:
PDGFRB
Uniprot ID:
P09619
Molecular weight:
123966.9
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:16497876 ]
  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:16436588 ]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [PubMed:20072833 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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. [PubMed:20423956 ]
  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. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662 ]
  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. doi: 10.1182/blood-2007-10-116236. Epub 2008 Jul 31. [PubMed:18669873 ]
General function:
Involved in ATP binding
Specific function:
Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular weight:
72313.5
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. [PubMed:20423956 ]
  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. doi: 10.1111/j.1476-5381.2009.00383.x. Epub 2009 Sep 28. [PubMed:19785662 ]

Only showing the first 10 proteins. There are 17 proteins in total.