Dasatinib

Identification

Summary

Dasatinib is a tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia.

Brand Names
Sprycel
Generic Name
Dasatinib
DrugBank Accession Number
DB01254
Background

Dasatinib is an orally available multikinase inhibitor indicated for the treatment of Philadelphia chromosome (Ph)-positive leukemias.1,7 Ph is a chromosomal abnormality found in patients with chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), where the ABL tyrosine kinase and the breakpoint cluster region (BCR) gene transcribe the chimeric protein BCR-ABL. BCR-ABL is associated with the uncontrolled activity of the ABL tyrosine kinase and is involved in the pathogenesis of CML and 15-30% of ALL cases.5,6 Dasatinib also inhibits a spectrum of kinases involved in cancer, including several SRC-family kinases.5

Unlike imatinib, another tyrosine kinase used for the treatment of CML and Ph-positive ALL, dasatinib inhibits the active and inactive conformations of the ABL kinase domain.2,5 Also, mutations in the kinase domain of BCR-ABL may lead to relapse during imatinib treatment. Since dasatinib does not interact with some of the residues involved in those mutations, the use of this drug represents a therapeutic alternative for patients with cancers that have developed imatinib-resistance.2 The use of dasatinib was first approved by the FDA in 2006.7,9

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 488.006
Monoisotopic: 487.155721508
Chemical Formula
C22H26ClN7O2S
Synonyms
  • Anh. dasatinib
  • Anhydrous dasatinib
  • BMS dasatinib
  • Dasatinib
  • Dasatinib (anh.)
  • dasatinib (anhydrous)
  • Dasatinib anhydrous
  • Dasatinibum
  • N-(2-CHLORO-6-methylphenyl)-2-({6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl}amino)-1,3-thiazole-5-carboxamide
External IDs
  • BMS-354825

Pharmacology

Indication

Dasatinib is indicated for the treatment of newly diagnosed adults with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, as well as adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib, and adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy. Dasatinib is also indicated for the treatment of pediatric patients 1 year of age and older with Ph+ CML in chronic phase or newly diagnosed Ph+ ALL in combination with chemotherapy.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAccelerated phase chronic myologenic leukemia••••••••••••••••••••••••••• •• ••••••••••• •• ••••• •••••••
Adjunct therapy in treatment ofAcute lymphoblastic leukemia•••••••••••••••••••••••••• •••••••••
Treatment ofAcute lymphoblastic leukemia••••••••••••••••••••••••••• •• ••••••••••• •• ••••• •••••••
Treatment ofChronic phase chronic myeloid leukemia••••••••••••••••••••••••••• •• ••••••••••• •• ••••• •••••••
Treatment ofMyeloid leukemia, chronic, chronic phase•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Dasatinib is an orally available small-molecule multikinase inhibitor.5 During clinical trials, less than 1% of patients treated with dasatinib had QTc prolongation as an adverse reaction, and 1% experienced a QTcF higher than 500 ms. The use of dasatinib is also associated with myelosuppression, bleeding-related events, fluid retention, cardiovascular toxicity, pulmonary arterial hypertension, severe dermatologic reactions, tumor lysis syndrome and hepatotoxicity. It may also cause embryo-fetal toxicity and lead to adverse reactions associated with bone growth and development in pediatric patients.7

Mechanism of action

Dasatinib is a tyrosine kinase inhibitor with several targets. At nanomolar concentrations, it inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ.1,5,7 In patients with chronic myeloid leukemia (CML), the tyrosine kinase activity of BCR-ABL is deregulated, leading to the growth, proliferation and survival of cancerous hematopoietic cells. Dasatinib binds to the active and inactive conformation of the ABL kinase domain with a higher affinity than imatinib.6 In chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines overexpressing BCR-ABL, dasatinib inhibits cell growth. Also, dasatinib has in vitro activity against leukemic cell lines that are either sensitive or resistant to imatinib.7 It has been suggested that dasatinib is able to overcome imatinib resistance caused by BCR-ABL kinase domain mutations because it does not require interaction with some of the residues involved in those mutations.6,7

TargetActionsOrganism
ATyrosine-protein kinase ABL1
inhibitor
multitarget
Humans
AProto-oncogene tyrosine-protein kinase Src
inhibitor
multitarget
Humans
AEphrin type-A receptor 2
antagonist
Humans
ATyrosine-protein kinase Lck
inhibitor
multitarget
Humans
ATyrosine-protein kinase Yes
inhibitor
Humans
AMast/stem cell growth factor receptor Kit
antagonist
Humans
APlatelet-derived growth factor receptor beta
antagonist
Humans
USignal transducer and activator of transcription 5B
inhibitor
Humans
UTyrosine-protein kinase ABL2
multitarget
Humans
ATyrosine-protein kinase Fyn
inhibitor
multitarget
Humans
UTyrosine-protein kinase BTK
inhibitor
Humans
UNuclear receptor subfamily 4 group A member 3
inhibitor
Humans
ABreakpoint cluster region protein
inhibitor
Humans
UTyrosine-protein kinase CSK
inhibitor
Humans
UEphrin type-A receptor 5
inhibitor
Humans
UEphrin type-B receptor 4
inhibitor
Humans
UTyrosine-protein kinase Fgr
inhibitor
Humans
UTyrosine-protein kinase FRK
binder
Humans
UHeat shock cognate 71 kDa protein
binder
Humans
UTyrosine-protein kinase Lyn
inhibitor
Humans
UMitogen-activated protein kinase kinase kinase MLT
binder
Humans
UMitogen-activated protein kinase 14
binder
Humans
UAmidophosphoribosyltransferase
binder
Humans
Absorption

Dasatinib has a dose-proportional pharmacokinetic profile and a linear elimination between 15 mg/day (0.15 times the lowest approved recommended dose) and 240 mg/day (1.7 times the highest approved recommended dose). At 100 mg once a day, dasatinib has a Cmax and AUC of 82.2 ng/mL and 397 ng/mL*hr, respectively. In healthy adult subjects given dasatinib as dispersed tablets in juice, the adjusted geometric mean ratio compared to intact tablets was 0.97 for Cmax, and 0.84 for AUC. The Tmax of dasatinib is between 0.5 and 6 hours following oral administration. Following a single dose of 100 mg, a high-fat meal increases the AUC of dasatinib by 14%.7

Volume of distribution

Dasatinib has an apparent volume of distribution of 2505 L.7

Protein binding

In vitro, the binding of dasatinib to human plasma proteins is approximately 96%.7

Metabolism

In humans, dasatinib is mainly metabolized by CYP3A4, although flavin-containing monooxygenase 3 (FMO3) and uridine diphosphate-glucuronosyltransferase (UGT) enzymes are also involved in the formation of dasatinib metabolites.7 Five pharmacologically active dasatinib metabolites have been identified: M4, M5, M6, M20 and M24. M4, M20, and M24 are mainly generated by CYP3A4, M5 is generated by FMO3, and M6 is generated by a cytosolic oxidoreductase.3,4 M4 is equipotent to dasatinib and represents approximately 5% of the AUC. However, it is unlikely to play a major role in the observed pharmacology of dasatinib.3,7 M5 and M6 are more than 10 times less active than dasatinib and are considered minor circulating metabolites.3

Hover over products below to view reaction partners

Route of elimination

Dasatinib is mainly eliminated via feces. Within 10 days, 4% of dasatinib is recovered in urine, while 85% is recovered in feces. Approximately 0.1% and 19% of the administered dasatinib dose was recovered unchanged in urine and feces, respectively, and the rest was recovered as metabolites.7

Half-life

The terminal half-life of dasatinib is 3-5 hours.7

Clearance

The clearance of dasatinib does not vary over time. Dasatinib has an apparent oral clearance of 363.8 L/hr.7

Adverse Effects
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Toxicity

Overdose cases with dasatinib occurred in isolated cases during clinical studies. Patients that received 280 mg of dasatinib per day for 1 week developed severe myelosuppression and bleeding. Since dasatinib is associated with severe myelosuppression, patients that ingest more than the recommended dosage should be monitored closely for myelosuppression and receive appropriate supportive treatment.7

Acute overdose in animals was associated with cardiotoxicity. In rodents, ventricular necrosis and valvular/ventricular/atrial hemorrhage were detected at single doses higher than or equal to 100 mg/kg (600 mg/m2). In monkeys receiving single doses higher than or equal to 10 mg/kg (120 mg/m2), there was a tendency for increased systolic and diastolic blood pressure.7 In rats, the oral LD50 of dasatinib is 50-100 mg/kg, and in monkeys, it is 25-45 mg/kg.8

Pathways
PathwayCategory
Dasatinib 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 Dasatinib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Dasatinib can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Dasatinib is combined with Abciximab.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Dasatinib.
AbirateroneThe serum concentration of Dasatinib can be increased when it is combined with Abiraterone.
Food Interactions
  • Avoid grapefruit products. Grapefruit may reduce the CYP3A4 metabolism of dasatinib, increasing its serum levels.
  • Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of dasatinib.
  • Take with or without food. High fat meals may increase the AUC of dasatinib by to 14%; however, the product label recommends taking dasatinib with or without food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Dasatinib monohydrateRBZ1571X5H863127-77-9XHXFZZNHDVTMLI-UHFFFAOYSA-N
Dasatinib monolauryl sulfateFY77PS0C4O2398469-56-0SWMPKFFMQAIAEW-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Dasatinib AccordTablet, film coated70 mgOralAccord Healthcare S.L.U.2022-05-042023-03-30EU flag
Dasatinib AccordTablet, film coated80 mgOralAccord Healthcare S.L.U.2022-05-042023-03-30EU flag
Dasatinib AccordTablet, film coated50 mgOralAccord Healthcare S.L.U.2022-05-042023-03-30EU flag
Dasatinib AccordTablet, film coated20 mgOralAccord Healthcare S.L.U.2022-05-042023-03-30EU flag
Dasatinib AccordTablet, film coated140 mgOralAccord Healthcare S.L.U.2022-05-042023-03-30EU flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-dasatinibTablet100 mgOralApotex Corporation2020-01-06Not applicableCanada flag
Apo-dasatinibTablet80 mgOralApotex Corporation2020-01-06Not applicableCanada flag
Apo-dasatinibTablet50 mgOralApotex Corporation2020-01-06Not applicableCanada flag
Apo-dasatinibTablet70 mgOralApotex Corporation2020-01-06Not applicableCanada flag
Apo-dasatinibTablet20 mgOralApotex Corporation2020-01-06Not applicableCanada flag

Categories

ATC Codes
L01EA02 — Dasatinib
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as aromatic anilides. These are aromatic compounds containing an anilide group in which the carboxamide group is substituted with an aromatic group. They have the general structure RNC(=O)R', where R= benzene, and R = aryl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Aromatic anilides
Alternative Parents
N-arylpiperazines / Thiazolecarboxamides / 2-heteroaryl carboxamides / Dialkylarylamines / 2,5-disubstituted thiazoles / Toluenes / Aminopyrimidines and derivatives / Chlorobenzenes / N-alkylpiperazines / 2-amino-1,3-thiazoles
show 14 more
Substituents
1,2-aminoalcohol / 1,3-thiazol-2-amine / 1,4-diazinane / 2,5-disubstituted 1,3-thiazole / 2-heteroaryl carboxamide / Alcohol / Alkanolamine / Amine / Amino acid or derivatives / Aminopyrimidine
show 36 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary amino compound, N-arylpiperazine, N-(2-hydroxyethyl)piperazine, aminopyrimidine, monocarboxylic acid amide, organochlorine compound, 1,3-thiazole, secondary amino compound (CHEBI:49375)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
X78UG0A0RN
CAS number
302962-49-8
InChI Key
ZBNZXTGUTAYRHI-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

References

Synthesis Reference
US6596746
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. [Article]
  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. [Article]
  3. Christopher LJ, Cui D, Wu C, Luo R, Manning JA, Bonacorsi SJ, Lago M, Allentoff A, Lee FY, McCann B, Galbraith S, Reitberg DP, He K, Barros A Jr, Blackwood-Chirchir A, Humphreys WG, Iyer RA: Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos. 2008 Jul;36(7):1357-64. doi: 10.1124/dmd.107.018267. Epub 2008 Apr 17. [Article]
  4. 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. [Article]
  5. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  6. Aguilera DG, Tsimberidou AM: Dasatinib in chronic myeloid leukemia: a review. Ther Clin Risk Manag. 2009 Apr;5(2):281-9. Epub 2009 May 4. [Article]
  7. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (February 2023) [Link]
  8. Bristol Myers Squibb: Dasatinib SDS [Link]
  9. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Human Metabolome Database
HMDB0015384
KEGG Drug
D03658
PubChem Compound
3062316
PubChem Substance
46505143
ChemSpider
2323020
BindingDB
13216
RxNav
1546019
ChEBI
49375
ChEMBL
CHEMBL1421
ZINC
ZINC000003986735
Therapeutic Targets Database
DAP000004
PharmGKB
PA162372878
PDBe Ligand
1N1
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dasatinib
PDB Entries
2gqg / 2y6o / 2zva / 3g5d / 3lfa / 3oht / 3qlg / 3sxr / 4qms / 4xey
show 11 more

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Bristol-Myers Squibb Co.
  • E.R. Squibb and Sons LLC
  • Physicians Total Care Inc.
Dosage Forms
FormRouteStrength
TabletOral100 mg
TabletOral20 mg
TabletOral50 mg
TabletOral70 mg
TabletOral80 mg
Tablet, film coatedOral111 MG
Tablet, film coatedOral16 MG
Tablet, film coatedOral40 MG
Tablet, film coatedOral55 MG
Tablet, film coatedOral63 MG
Tablet, film coatedOral79 MG
Tablet, film coatedOral140 MG
Tablet, film coatedOral50 MG
Tablet, film coatedOral
Powder, for suspensionOral10 MG/ML
TabletOral100 mg/1
TabletOral140 mg/1
TabletOral20 mg/1
TabletOral20.000 mg
TabletOral50 mg/1
TabletOral70 mg/1
TabletOral80 mg/1
Tablet, coatedOral100 mg
Tablet, coatedOral140 mg
Tablet, coatedOral14000000 mg
Tablet, coatedOral20 mg
Tablet, coatedOral50 mg
Tablet, coatedOral70 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral50 mg per tab
Tablet, film coatedOral70 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral80 mg
TabletOral140 mg
Prices
Unit descriptionCostUnit
Sprycel 100 mg tablet278.24USD tablet
Sprycel 50 mg tablet139.12USD tablet
Sprycel 70 mg tablet139.12USD tablet
Sprycel 20 mg tablet69.56USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2366932No2009-08-252020-04-12Canada flag
US6596746Yes2003-07-222020-12-28US flag
US7125875Yes2006-10-242020-10-13US flag
US7153856Yes2006-12-262020-10-28US flag
US7491725Yes2009-02-172026-09-28US flag
US8680103Yes2014-03-252025-08-04US flag
US11324745No2021-01-222041-01-22US flag
US11202778No2021-01-222041-01-22US flag
US11298356No2021-01-222041-01-22US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)280-286 °CFDA label
logP1.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0128 mg/mLALOGPS
logP2.77ALOGPS
logP4.01Chemaxon
logS-4.6ALOGPS
pKa (Strongest Acidic)10.99Chemaxon
pKa (Strongest Basic)7.19Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area106.51 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity133.08 m3·mol-1Chemaxon
Polarizability50.39 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9852
Blood Brain Barrier-0.507
Caco-2 permeable-0.5638
P-glycoprotein substrateSubstrate0.6562
P-glycoprotein inhibitor IInhibitor0.5371
P-glycoprotein inhibitor IIInhibitor0.5425
Renal organic cation transporterNon-inhibitor0.7288
CYP450 2C9 substrateNon-substrate0.7061
CYP450 2D6 substrateNon-substrate0.8152
CYP450 3A4 substrateSubstrate0.5704
CYP450 1A2 substrateNon-inhibitor0.5612
CYP450 2C9 inhibitorInhibitor0.8008
CYP450 2D6 inhibitorNon-inhibitor0.8358
CYP450 2C19 inhibitorInhibitor0.574
CYP450 3A4 inhibitorInhibitor0.7295
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8343
Ames testNon AMES toxic0.7185
CarcinogenicityNon-carcinogens0.7308
BiodegradationNot ready biodegradable0.9863
Rat acute toxicity2.4772 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8538
hERG inhibition (predictor II)Inhibitor0.718
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-MSsplash10-0a4j-3104900000-19c063b36c545a5eb85a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000m-0390000000-8a413cb9e53d14cbe10a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0011900000-4dac51b915117532ebe0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0000900000-e6c290f5261b658ed476
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-01bi-1000900000-46555aece3c129ee5b56
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000j-0004900000-a058ca25239583f03c28
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001u-6112900000-cabcedd96d1c222440b1
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-0137900000-b0c704468310278fc98b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f8c-8073900000-48ff0ba1dab46f900278
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]-234.1197177
predicted
DarkChem Lite v0.1.0
[M-H]-199.48085
predicted
DeepCCS 1.0 (2019)
[M+H]+235.0765177
predicted
DarkChem Lite v0.1.0
[M+H]+201.83887
predicted
DeepCCS 1.0 (2019)
[M+Na]+233.6422177
predicted
DarkChem Lite v0.1.0
[M+Na]+208.10109
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Multitarget
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. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Multitarget
General Function
Sh3/sh2 adaptor activity
Specific Function
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion recept...
Gene Name
SRC
Uniprot ID
P12931
Uniprot Name
Proto-oncogene tyrosine-protein kinase Src
Molecular Weight
59834.295 Da
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Details
3. Ephrin type-A receptor 2
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. Th...
Gene Name
EPHA2
Uniprot ID
P29317
Uniprot Name
Ephrin type-A receptor 2
Molecular Weight
108265.585 Da
References
  1. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  2. Christopher LJ, Cui D, Wu C, Luo R, Manning JA, Bonacorsi SJ, Lago M, Allentoff A, Lee FY, McCann B, Galbraith S, Reitberg DP, He K, Barros A Jr, Blackwood-Chirchir A, Humphreys WG, Iyer RA: Metabolism and disposition of dasatinib after oral administration to humans. Drug Metab Dispos. 2008 Jul;36(7):1357-64. doi: 10.1124/dmd.107.018267. Epub 2008 Apr 17. [Article]
  3. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Multitarget
General Function
Sh2 domain binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells. Plays a key role in T-ce...
Gene Name
LCK
Uniprot ID
P06239
Uniprot Name
Tyrosine-protein kinase Lck
Molecular Weight
58000.15 Da
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. [Article]
  2. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  3. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by rece...
Gene Name
YES1
Uniprot ID
P07947
Uniprot Name
Tyrosine-protein kinase Yes
Molecular Weight
60800.78 Da
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. [Article]
  2. Margutti S, Laufer SA: Are MAP kinases drug targets? Yes, but difficult ones. ChemMedChem. 2007 Aug;2(8):1116-40. [Article]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  4. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
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. 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. [Article]
  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. [Article]
  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. 2008 Jan;107(2):303. Epub 2007 Mar 10. [Article]
  4. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
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. Zhang Z, Meier KE: New assignments for multitasking signal transduction inhibitors. Mol Pharmacol. 2006 May;69(5):1510-2. Epub 2006 Feb 23. [Article]
  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. [Article]
  3. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  4. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcription factor activity, sequence-specific dna binding
Specific Function
Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activa...
Gene Name
STAT5B
Uniprot ID
P51692
Uniprot Name
Signal transducer and activator of transcription 5B
Molecular Weight
89865.35 Da
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Multitarget
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, ce...
Gene Name
ABL2
Uniprot ID
P42684
Uniprot Name
Abelson tyrosine-protein kinase 2
Molecular Weight
128341.935 Da
References
  1. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  2. Hantschel O, Rix U, Schmidt U, Burckstummer T, Kneidinger M, Schutze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G: The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13283-8. Epub 2007 Aug 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Multitarget
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remode...
Gene Name
FYN
Uniprot ID
P06241
Uniprot Name
Tyrosine-protein kinase Fyn
Molecular Weight
60761.49 Da
References
  1. Lindauer M, Hochhaus A: Dasatinib. Recent Results Cancer Res. 2010;184:83-102. doi: 10.1007/978-3-642-01222-8_7. [Article]
  2. Lee D, Park YH, Lee JE, Kim HS, Min KY, Jo MG, Kim HS, Choi WS, Kim YM: Dasatinib Inhibits Lyn and Fyn Src-Family Kinases in Mast Cells to Suppress Type I Hypersensitivity in Mice. Biomol Ther (Seoul). 2020 Sep 1;28(5):456-464. doi: 10.4062/biomolther.2020.013. [Article]
  3. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately le...
Gene Name
BTK
Uniprot ID
Q06187
Uniprot Name
Tyrosine-protein kinase BTK
Molecular Weight
76280.71 Da
References
  1. Hantschel O, Rix U, Schmidt U, Burckstummer T, Kneidinger M, Schutze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G: The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13283-8. Epub 2007 Aug 7. [Article]
  2. Kaliamurthi S, Selvaraj G, Selvaraj C, Singh SK, Wei DQ, Peslherbe GH: Structure-Based Virtual Screening Reveals Ibrutinib and Zanubrutinib as Potential Repurposed Drugs against COVID-19. Int J Mol Sci. 2021 Jun 30;22(13). pii: ijms22137071. doi: 10.3390/ijms22137071. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vascular smooth muscle, myeloid progenitor cell and type B pancreatic cells; promotes mitogen-induced vascular smooth muscle cell proliferation through transactivation of SKP2 promoter by binding a NBRE site (By similarity). Upon PDGF stimulation, stimulates vascular smooth muscle cell proliferation by regulating CCND1 and CCND2 expression. In islets, induces type B pancreatic cell proliferation through up-regulation of genes that activate cell cycle, as well as genes that cause degradation of the CDKN1A (By similarity). Negatively regulates myeloid progenitor cell proliferation by repressing RUNX1 in a NBRE site-independent manner. During inner ear, plays a role as a key mediator of the proliferative growth phase of semicircular canal development (By similarity). Mediates also survival of neuron and smooth muscle cells; mediates CREB-induced neuronal survival, and during hippocampus development, plays a critical role in pyramidal cell survival and axonal guidance. Is required for S phase entry of the cell cycle and survival of smooth muscle cells by inducing CCND1, resulting in RB1 phosphorylation. Binds to NBRE motif in CCND1 promoter, resulting in the activation of the promoter and CCND1 transcription (By similarity). Plays also a role in inflammation; upon TNF stimulation, mediates monocyte adhesion by inducing the expression of VCAM1 and ICAM1 by binding to the NBRE consensus site (By similarity) (PubMed:20558821). In mast cells activated by Fc-epsilon receptor cross-linking, promotes the synthesis and release of cytokines but impairs events leading to degranulation (By similarity). Plays also a role in metabolism; by modulating feeding behavior; and by playing a role in energy balance by inhibiting the glucocorticoid-induced orexigenic neuropeptides AGRP expression, at least in part by forming a complex with activated NR3C1 on the AGRP- glucocorticoid response element (GRE), and thus weakening the DNA binding activity of NR3C1. Upon catecholamines stimulation, regulates gene expression that controls oxidative metabolism in skeletal muscle (By similarity). Plays a role in glucose transport by regulating translocation of the SLC2A4 glucose transporter to the cell surface (PubMed:24022864). Finally, during gastrulation plays a crucial role in the formation of anterior mesoderm by controlling cell migration. Inhibits adipogenesis (By similarity). Also participates in cardiac hypertrophy by activating PARP1 (By similarity).
Specific Function
Core promoter sequence-specific dna binding
Gene Name
NR4A3
Uniprot ID
Q92570
Uniprot Name
Nuclear receptor subfamily 4 group A member 3
Molecular Weight
68229.025 Da
References
  1. Hantschel O, Rix U, Schmidt U, Burckstummer T, Kneidinger M, Schutze G, Colinge J, Bennett KL, Ellmeier W, Valent P, Superti-Furga G: The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci U S A. 2007 Aug 14;104(33):13283-8. Epub 2007 Aug 7. [Article]
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. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL: Overriding imatinib resistance with a novel ABL kinase inhibitor. Science. 2004 Jul 16;305(5682):399-401. [Article]
  2. 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]
  3. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  4. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C...
Gene Name
CSK
Uniprot ID
P41240
Uniprot Name
Tyrosine-protein kinase CSK
Molecular Weight
50703.975 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  2. Kwarcinski FE, Fox CC, Steffey ME, Soellner MB: Irreversible inhibitors of c-Src kinase that target a nonconserved cysteine. ACS Chem Biol. 2012 Nov 16;7(11):1910-7. doi: 10.1021/cb300337u. Epub 2012 Sep 5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane-ephrin receptor activity
Specific Function
Receptor tyrosine kinase which binds promiscuously GPI-anchored ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The ...
Gene Name
EPHA5
Uniprot ID
P54756
Uniprot Name
Ephrin type-A receptor 5
Molecular Weight
114802.31 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  2. Wang X, Zhang M, Ping F, Liu H, Sun J, Wang Y, Shen A, Ding J, Geng M: Identification and Therapeutic Intervention of Coactivated Anaplastic Lymphoma Kinase, Fibroblast Growth Factor Receptor 2, and Ephrin Type-A Receptor 5 Kinases in Hepatocellular Carcinoma. Hepatology. 2019 Feb;69(2):573-586. doi: 10.1002/hep.29792. Epub 2018 Mar 24. [Article]
Details
16. Ephrin type-B receptor 4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The...
Gene Name
EPHB4
Uniprot ID
P54760
Uniprot Name
Ephrin type-B receptor 4
Molecular Weight
108269.26 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  2. Aslam MI, Abraham J, Mansoor A, Druker BJ, Tyner JW, Keller C: PDGFRbeta reverses EphB4 signaling in alveolar rhabdomyosarcoma. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6383-8. doi: 10.1073/pnas.1403608111. Epub 2014 Apr 14. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocy...
Gene Name
FGR
Uniprot ID
P09769
Uniprot Name
Tyrosine-protein kinase Fgr
Molecular Weight
59478.11 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  2. 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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Receptor binding
Specific Function
Non-receptor tyrosine-protein kinase that negatively regulates cell proliferation. Positively regulates PTEN protein stability through phosphorylation of PTEN on 'Tyr-336', which in turn prevents i...
Gene Name
FRK
Uniprot ID
P42685
Uniprot Name
Tyrosine-protein kinase FRK
Molecular Weight
58253.61 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Unfolded protein binding
Specific Function
Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of CITED1 on Smad-mediated transcription. Chaperone. Component of the PRP19-CDC5L complex that f...
Gene Name
HSPA8
Uniprot ID
P11142
Uniprot Name
Heat shock cognate 71 kDa protein
Molecular Weight
70897.565 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Receptor signaling protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, respons...
Gene Name
LYN
Uniprot ID
P07948
Uniprot Name
Tyrosine-protein kinase Lyn
Molecular Weight
58573.595 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
  2. Lee D, Park YH, Lee JE, Kim HS, Min KY, Jo MG, Kim HS, Choi WS, Kim YM: Dasatinib Inhibits Lyn and Fyn Src-Family Kinases in Mast Cells to Suppress Type I Hypersensitivity in Mice. Biomol Ther (Seoul). 2020 Sep 1;28(5):456-464. doi: 10.4062/biomolther.2020.013. [Article]
  3. FDA Approved Drug Products: Sprycel (dasatinib) tablets for oral use (June 2006) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Protein serine/threonine kinase activity
Specific Function
Stress-activated component of a protein kinase signal transduction cascade. Regulates the JNK and p38 pathways. Pro-apoptotic. Role in regulation of S and G2 cell cycle checkpoint by direct phospho...
Gene Name
ZAK
Uniprot ID
Q9NYL2
Uniprot Name
Mitogen-activated protein kinase kinase kinase MLT
Molecular Weight
91154.315 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Protein serine/threonine kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK14 is one of the four p38 MAPKs which play an important role in the cascades of cellu...
Gene Name
MAPK14
Uniprot ID
Q16539
Uniprot Name
Mitogen-activated protein kinase 14
Molecular Weight
41292.885 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Metal ion binding
Specific Function
Not Available
Gene Name
PPAT
Uniprot ID
Q06203
Uniprot Name
Amidophosphoribosyltransferase
Molecular Weight
57398.52 Da
References
  1. Kneidinger M, Schmidt U, Rix U, Gleixner KV, Vales A, Baumgartner C, Lupinek C, Weghofer M, Bennett KL, Herrmann H, Schebesta A, Thomas WR, Vrtala S, Valenta R, Lee FY, Ellmeier W, Superti-Furga G, Valent P: The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107. doi: 10.1182/blood-2007-08-104372. Epub 2008 Jan 7. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-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
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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
CYP1B1
Uniprot ID
Q16678
Uniprot Name
Cytochrome P450 1B1
Molecular Weight
60845.33 Da
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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
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. 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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine 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 impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
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. [Article]
Details
6. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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. [Article]
  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. [Article]
  3. Dasatinib FDA label [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
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. 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]
  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. [Article]

Drug created at May 09, 2007 00:32 / Updated at May 25, 2024 22:42