imatinib   

GtoPdb Ligand ID: 5687

Synonyms: CGP 57148 | Gleevec® | Glivec® | STI571
imatinib is an approved drug (FDA & EMA (2001))
Compound class: Synthetic organic
Comment: Imatinib is a Type-2 kinase inhibitor. Its main inhibitory activity is against ABL kinase, but it has significant action at secondary targets including platelet-derived growth factor receptor (PDGFR) and stem cell growth factor receptor (KIT).

Coronavirus: imatinib is reported to block Spike protein-induced SARS-CoV and MERS-CoV fusion in vitro [8], potentially by blocking Abl2 at the endosomal membrane and disrupting the actin dynamics that are required for virus-host fusion [2]. It will be informative to determine if this holds true for SARS-CoV-2, and whether re-purposing of imatinib and/or newer Abl kinase inhibitors (dasatinib, bosutinib, ponatinib, nilotinib) could be a viable strategy against COVID-19. This approach would likely to be most effective during the early stage of infection.
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2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 86.28
Molecular weight 493.26
XLogP 3.04
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CN1CCN(CC1)Cc1ccc(cc1)C(=O)Nc1ccc(c(c1)Nc1nccc(n1)c1cccnc1)C
Isomeric SMILES CN1CCN(CC1)Cc1ccc(cc1)C(=O)Nc1ccc(c(c1)Nc1nccc(n1)c1cccnc1)C
InChI InChI=1S/C29H31N7O/c1-21-5-10-25(18-27(21)34-29-31-13-11-26(33-29)24-4-3-12-30-19-24)32-28(37)23-8-6-22(7-9-23)20-36-16-14-35(2)15-17-36/h3-13,18-19H,14-17,20H2,1-2H3,(H,32,37)(H,31,33,34)
InChI Key KTUFNOKKBVMGRW-UHFFFAOYSA-N
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. Coleman CM, Sisk JM, Mingo RM, Nelson EA, White JM, Frieman MB. (2016)
Abelson Kinase Inhibitors Are Potent Inhibitors of Severe Acute Respiratory Syndrome Coronavirus and Middle East Respiratory Syndrome Coronavirus Fusion.
J. Virol., 90 (19): 8924-33. [PMID:27466418]
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. 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]
5. Horio T, Hamasaki T, Inoue T, Wakayama T, Itou S, Naito H, Asaki T, Hayase H, Niwa T. (2007)
Structural factors contributing to the Abl/Lyn dual inhibitory activity of 3-substituted benzamide derivatives.
Bioorg. Med. Chem. Lett., 17 (10): 2712-7. [PMID:17376680]
6. Kim HG, Tan L, Weisberg EL, Liu F, Canning P, Choi HG, Ezell SA, Wu H, Zhao Z, Wang J et al.. (2013)
Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor.
ACS Chem. Biol., 8 (10): 2145-50. [PMID:23899692]
7. Rhee CK, Kim JW, Park CK, Kim JS, Kang JY, Kim SJ, Kim SC, Kwon SS, Kim YK, Park SH et al.. (2011)
Effect of imatinib on airway smooth muscle thickening in a murine model of chronic asthma.
Int. Arch. Allergy Immunol., 155 (3): 243-51. [PMID:21293142]
8. Sisk JM, Frieman MB, Machamer CE. (2018)
Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors.
J. Gen. Virol., 99 (5): 619-630. [PMID:29557770]
9. Takeuchi K, Koike K, Kamijo T, Ishida S, Nakazawa Y, Kurokawa Y, Sakashita K, Kinoshita T, Matsuzawa S, Shiohara M et al.. (2003)
STI571 inhibits growth and adhesion of human mast cells in culture.
J. Leukoc. Biol., 74 (6): 1026-34. [PMID:12960256]
10. Ustun C, DeRemer DL, Akin C. (2011)
Tyrosine kinase inhibitors in the treatment of systemic mastocytosis.
Leuk. Res., 35 (9): 1143-52. [PMID:21641642]
11. 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]