Imatinib

DB00619ApprovedInvestigationalSmall moleculeKinase Inhibitor

Imatinib is a tyrosine kinase inhibitor used to treat a number of leukemias, myelodysplastic/myeloproliferative disease, systemic mastocytosis, hypereosinophilic syndrome, dermatofibrosarcoma protuberans, and gastrointestinal stromal tumors. Imatinib is a small molecule kinase inhibitor that revolutionized the treatment of cancer, particularly chronic myeloid leukemia, in 2001.

Mechanism: Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the BCR-ABL tyrosine kinase, the constitutively active tyrosine kinase created by the Philadelphia chromosome abnormality in CML. Although the function of normal BCR is still unclear, ABL activation is overexpressed in various tumors and is heavily implicated in cancer cells growth and survival. Imatinib inhibits the BCR-ABL protein by binding to the ATP pocket in the active site, thus preventing downstream phosphorylation of target protein.
Imatinib is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib inhibits proliferation and induces apoptosis in GIST cells, which express an activating c-Kit mutation.
Curator reviewed · 5 references
Primary indication: Imatinib is indicated for the treatment of adult and pediatric chronic myeloid leukemia with Philadelphia chromosome mutation (Ph+) in blast crisis, accelerated phase, or chronic phase after IFN-alpha therapy failure.Curator reviewed · 23 structured indications
Formula / weight: C₂₉H₃₁N₇O · 493.6027 g/mol (avg)
First approval: Canada, 2003 · United States, 2001 · European Union, 2016
Code names: CGP-57148 · CGP-57148B · QTI-571
Brand names: Gleevec
Glivec
Imatinib Teva
Imkeldi