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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. 
Ligand Activity Visualisation ChartsThese 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 more information in the IUPHAR Pharmacology Education Project: imatinib |
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Summary of Clinical Use  |
| Used in the treatment of multiple cancers including chronic myelogenous leukemia and gastrointestinal stromal tumours (GIST). Adjuvant imatinib is recommended for KIT-mutated GISTs. The clinically administered form is the Imatinib mesilate (mesylate) salt (PubChem CID 123596). Generic imatinib mesylate tablets were approved by the US FDA in December 2015, as therapeutic equivalents of Novartis' original Gleevec. |
| Mechanism Of Action and Pharmacodynamic Effects |
| Imatinib is a protein-tyrosine kinase inhibitor that inhibits proliferation and induces apoptosis in Bcr-Abl leukemic cells from Philadelphia chromosome positive chronic myeloid leukemia (CML) and as such is an antineoplastic agent. Imatinib acts to reduce the abnormal constitutive activity of Bcr-Abl tyrosine kinase in CML. Additional imatinib targets include the tyrosine kinase receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF, c-Kit) where it has been shown to inhibit PDGF- and SCF-mediated cellular events. |
| Pharmacokinetics |
| Absorption/Distribution |
| Imatinib is well absorbed (peaking 2-4h after administration) with bioavailability reaching 98%. 95% of circulating imatinib is protein bound. |
| Biotransformation/Metabolism |
| CYP4A4 in the liver is the major metabolic enzyme converting imatinib to its main circulating (and active) derivative, N-demethylated piperazine. CYP1A2, CYP2D6, CYP2C9, and CYP2C19, play minor roles in its metabolism. |
| Elimination |
| Imatinib excretion, mainly as metabolites, is predominately in the feces (68%) with a minor amount eliminated in the urine (13%). |
| Population pharmacokinetics |
| No clinically significant change in pharmacokinetics due to age, weight or gender has been reported and in children pharmacokinetics are similar to those in adults. |
| Organ function impairment |
| Patients with severe renal impairment may show raised exposure to imatinib and its metabolites compared to patients with healthy renal function, as do patients with severe hepatic impairment. |
| External links |
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For extended ADME data see the following: Electronic Medicines Compendium (eMC) Drugs.com European Medicines Agency (EMA) |
