Canertinib (CI-1033, PD-183805)

Canertinib is an irreversible tyrosine kinase inhibitor. It not only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent intracellular destruction of ErbB-2 molecules.  Canertinib alkylates a cysteine residue specific to ErbB receptors.  The degradative pathway of ErbB receptor tyrosine kinases stimulated by tyrosine kinase inhibitors appears to be chaperone mediated, and thus is similar to the pathways activated by the heat shock protein 90 (Hsp90) antagonist geldanamycin and by stress-induced mechanisms.