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].
Click here for help

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.

✖

View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: dasatinib

dasatinib is commercially available from our sponsors

2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

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.

✖
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
Click here for help

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/)

✖
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/)
References
1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011)
Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]
2. Ansari MM, Ghosh M, Lee DS, Son YO. (2024)
Senolytic therapeutics: An emerging treatment modality for osteoarthritis.
Ageing Res Rev, 96: 102275. [PMID:38494091]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
4. Farr JN, Atkinson EJ, Achenbach SJ, Volkman TL, Tweed AJ, Vos SJ, Ruan M, Sfeir J, Drake MT, Saul D et al.. (2024)
Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial.
Nat Med, 30 (9): 2605-2612. [PMID:38956196]
5. FDA. 
FDA approves dasatinib for pediatric patients with CML.
Accessed on 13/11/2017. Modified on 13/11/2017. fda.gov, https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm584725.htm?utm_campaign=Oncology%2011%2F13&utm_medium=email&utm_source=Eloqua&elqTrackId=e3fc8b51cc174a8eaf2296d2df9e04e1&elq=8e01e0f3ebc34cdbb393be86aa2995d4&elqaid=1301&elqat=1&elqCampaignId=784
6. Fekete M, Major D, Feher A, Fazekas-Pongor V, Lehoczki A. (2024)
Geroscience and pathology: a new frontier in understanding age-related diseases.
Pathol Oncol Res, 30: 1611623. [PMID:38463143]
7. Ferreira C, Vieira P, Sá H, Malva J, Castelo-Branco M, Reis F, Viana S. (2024)
Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases.
Front Immunol, 15: 1360065. [PMID:38558823]
8. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013)
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
Biochem J, 451 (2): 313-28. [PMID:23398362]
9. Guo X, Wen S, Wang J, Zeng X, Yu H, Chen Y, Zhu X, Xu L. (2024)
Senolytic combination of dasatinib and quercetin attenuates renal damage in diabetic kidney disease.
Phytomedicine, 130: 155705. [PMID:38761776]
10. Kitagawa D, Yokota K, Gouda M, Narumi Y, Ohmoto H, Nishiwaki E, Akita K, Kirii Y. (2013)
Activity-based kinase profiling of approved tyrosine kinase inhibitors.
Genes Cells, 18 (2): 110-22. [PMID:23279183]
11. O'Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, Cowan-Jacob SW, Lee FY, Heinrich MC, Deininger MW et al.. (2005)
In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants.
Cancer Res, 65 (11): 4500-5. [PMID:15930265]
12. Ozanne J, Prescott AR, Clark K. (2015)
The clinically approved drugs dasatinib and bosutinib induce anti-inflammatory macrophages by inhibiting the salt-inducible kinases.
Biochem J, 465 (2): 271-9. [PMID:25351958]
13. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]
14. Zhang P, Kishimoto Y, Grammatikakis I, Gottimukkala K, Cutler RG, Zhang S, Abdelmohsen K, Bohr VA, Misra Sen J, Gorospe M et al.. (2019)
Senolytic therapy alleviates Aβ-associated oligodendrocyte progenitor cell senescence and cognitive deficits in an Alzheimer's disease model.
Nat Neurosci, 22 (5): 719-728. [PMID:30936558]
15. Zhao Q, Ren C, Liu L, Chen J, Shao Y, Sun N, Sun R, Kong Y, Ding X, Zhang X et al.. (2019)
Discovery of SIAIS178 as an Effective BCR-ABL Degrader by Recruiting Von Hippel-Lindau (VHL) E3 Ubiquitin Ligase.
J Med Chem, 62 (20): 9281-9298. [PMID:31539241]
16. Zheng L, He S, Wang H, Li J, Liu Y, Liu S. (2024)
Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.
Aging Dis, 15 (6): 2554-2594. [PMID:38421832]
17. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, Palmer AK, Ikeno Y, Hubbard GB, Lenburg M et al.. (2015)
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.
Aging Cell, 14 (4): 644-58. [PMID:25754370]