Drug Class: Tyrosine kinase inhibitor (TKI)
Mechanism of Action
- Selectively inhibits BCR-ABL tyrosine kinase, the abnormal protein produced by the Philadelphia chromosome.
- Also inhibits c-KIT and PDGFR tyrosine kinases.
- Blocks ATP binding site → prevents phosphorylation and downstream signaling.
- Result: Inhibits cancer cell proliferation and promotes apoptosis.
Clinical Indications
- Chronic Myeloid Leukemia (CML) – first-line treatment for chronic phase
- Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL)
- Gastrointestinal Stromal Tumors (GIST) – with c-KIT mutations
- Systemic mastocytosis (rare cases with PDGFR mutation)
- Hypereosinophilic syndrome and some myelodysplastic/myeloproliferative neoplasms
Major Side Effects
- Fluid retention (periorbital or peripheral edema)
- Nausea, vomiting, diarrhea
- Muscle cramps and myalgias
- Hepatotoxicity (↑ liver enzymes)
- Myelosuppression (anemia, neutropenia, thrombocytopenia)
- Rash and skin reactions
Key Pharmacologic Properties
- Oral administration
- Metabolized by CYP3A4 (watch for drug interactions!)
- Long half-life: ~18 hours
- Requires daily dosing
- Therapeutic monitoring: PCR for BCR-ABL transcript levels in CML
Synonyms
Gleevec