imatinib

Ligand id: 5687

Name: imatinib

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Structure and Physico-chemical Properties

2D Structure
Calculated 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 4.27
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

No information available.
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.
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