Target tyrosine kinases / Inhibit Bcr-Abl / Mechanism
STIs that target Bcr-Abl: DASATINIB, IMATINIB, NILOTINIB
Mechanisms of action
DASATANIB, IMATINIB (Gleevec), NILOTINIB- competitive antagonists of the ATP-binding site of:
- bcr-abl, the non-receptor tyrosine kinase whose activity is deregulated by the translocation of its gene from chromosome 9 to chromosome 22 in most patients with CML
- also target c-kit, the tyrosine kinase altered in gastrointestinal stromal tumours (GIST), and are weak antagonists of the platelet-derived growth factor (PDGF) receptor
- DASTAINIB also targets Src, a tyrosine kinase whose expression is upregulated in several types of cancer
- may be anti-metastatic in epithelial-derived tumours