Small molecule
PubChem CID 5291
Imatinib
Gleevec
- Mechanism of action
- BCR-ABL tyrosine kinase inhibitor
- In plain language
- Blocks the activity of an abnormal enzyme that drives growth in certain leukemia cells and several other kinase-driven cancers, stopping them from multiplying.
- How it works
- Imatinib is a small-molecule tyrosine kinase inhibitor that binds within the ATP-binding pocket of the BCR-ABL fusion protein, as well as the related kinases PDGFR and KIT, locking each in an inactive conformation. This blocks ATP from engaging the kinase, preventing it from phosphorylating downstream substrates and effectively switching off the signaling cascade the kinase would otherwise drive. In BCR-ABL-positive cells this loss of signaling halts proliferation of the Philadelphia-chromosome-positive clone and induces apoptosis; in KIT- or PDGFR-driven tumors such as GIST, the same competitive inhibition removes the constitutive growth signal sustaining the tumor. Because the drug targets the specific molecular driver of each disease rather than dividing cells generally, it is classified as a targeted therapy rather than conventional cytotoxic chemotherapy.
- Therapeutic applications
- Imatinib is FDA-approved for multiple Philadelphia-chromosome-positive (Ph+) and kinase-driven malignancies: newly diagnosed and relapsed/refractory Ph+ chronic myeloid leukemia (chronic, accelerated, and blast phase) in adults and children; relapsed or refractory Ph+ acute lymphoblastic leukemia (adults) and newly diagnosed Ph+ ALL in combination with chemotherapy (pediatric); myelodysplastic/myeloproliferative disease associated with PDGFR gene rearrangements; aggressive systemic mastocytosis without the D816V c-Kit mutation; hypereosinophilic syndrome and/or chronic eosinophilic leukemia; unresectable, recurrent, or metastatic dermatofibrosarcoma protuberans; and Kit-positive gastrointestinal stromal tumors (GIST), both as treatment for metastatic/unresectable disease and as adjuvant therapy after surgical resection.
- Class
- Small molecule
- Therapeutic area
- Oncology
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