dasatinib   Click here for help

GtoPdb Ligand ID: 5678

Synonyms: BMS 345825 | BMS 354825 | BMS 35482513 | Sprycel®
Approved drug PDB Ligand Immunopharmacology Ligand
dasatinib is an approved drug (FDA & EMA (2006))
Compound class: Synthetic organic
Comment: Dasatinib is a Type-1 kinase inhibitor and was first approved by the FDA in 2006.
A combination of dasatinib and quercetin has been investigated in animal models for senolytic activity [9,14,17]. Senolytic agents are intended to reduce the abundance of senescent cells as a mechanism to treat age-related diseases, reduce frailty and extend healthy lifespan [2,6-7,16].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: dasatinib

dasatinib is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 134.75
Molecular weight 487.16
XLogP 1.99
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OCCN1CCN(CC1)c1cc(nc(n1)C)Nc1ncc(s1)C(=O)Nc1c(C)cccc1Cl
Isomeric SMILES OCCN1CCN(CC1)c1cc(nc(n1)C)Nc1ncc(s1)C(=O)Nc1c(C)cccc1Cl
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)
InChI Key ZBNZXTGUTAYRHI-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML), including pediatric patients in the US as of November 2017 [5]. A Phase 2 clinical trial (NCT01467986) assessing dasatinib as a component of a multimodal molecular therapy to treat relapsed or refractory high-risk neuroblastoma is currently ongoing (Oct 2014).
Snnolytic activity: Results of a phase 2 RCT to evaluate the effect of dasatinib plus quercetin on bone metabolism in postmenopausal women were published in 2024 [4].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Dasatinib inhibits growth of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress the kinase BCR-ABL. Dasatinib also inhibits the following kinases at nanomolar concentrations: SRC family kinases (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. In vitro, dasatinib is active against leukaemic cell lines expressing variants of imatinib-sensitive and resistant disease and research shows that dasatinib can overcome imatinib resistance resulting from BCR-ABL overexpression, BCR-ABL kinase domain mutations, activation of alternate signalling pathways involving the SRC family kinases (LYN, HCK), and multidrug resistance gene overexpression.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT04313634 Targeting Cellular Senescence With Senolytics to Improve Skeletal Health in Older Humans Phase 2 Interventional Mayo Clinic In this study dasatinib + quercetin was most effective (evaluating skeletal response in terms of change in the bone resorption marker C-terminal telopeptide of type 1 collagen) in participants with the highest senescent cell burden. 4
Pharmacokinetics Click here for help
Absorption/Distribution
Oral dose of dasatinib reaches peak circulatory concentration after 0.5-3h. Protein binding is 96% and for the active metabolite, 93%.
Biotransformation/Metabolism
Extensively metabolized by CYP3A4 to an active metabolite, which is equipotent to dasatinib but also by flavin-containing monooxygenase-3 and uridine diphosphate-glucuronosyltransferase enzymes.
Elimination
Elimination is primarily via the feces (85%). Only 4% of dasatinib and its metabolites are excreted via the kidney.
Population pharmacokinetics
No significant differences in the pharmacokinetics of dasatinib have been associated with age or gender. Safety and efficacy of dasatinib have not yet been studied in paediatric patients.
Organ function impairment
There are no studies in patients with impaired renal function; however, only 4% of the drug and its metabolites are excreted by the kidney. Studies in patients with varying levels of hepatic impairement suggest that dose adjustment is not necessary in these patients.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)