tcsc0263 Canertinib (dihydrochloride)

Canertinib dihydrochloride (CI-1033;PD-183805) is a potent and irreversible EGFR inhibitor; inhibits cellular EGFR and ErbB2 autophosphorylation with IC₅₀s of 7.4 and 9 nM.

IC50 & Target: IC50: 7.4 nM (EGFR), 9 nM (ErbB2)^[1]

In Vitro: Canertinib significantly inhibits growth of cultured melanoma cells, RaH3 and RaH5, in a dose-dependent manner. IC₅₀ is approximately 0.8 μM and by 5μM both cell lines are completely growth-arrested within 72 h of treatment. Incubation of exponentially growing RaH3 and RaH5 with 1 μM canertinib accumulated the cells in the G1-phase of the cell cycle within 24 h of treatment without induction of apoptosis. 1 μM canertinib inhibits ErbB1-3 receptor phosphorylation with a concomitant decrease of Akt-, Erk1/2- and Stat3 activity in both cell lines^[2].

In Vivo: Canertinib shows superior in vivo antitumor activity, giving growth delays in A431 xenografts exceeding 50 days following oral administration^[1]. The growth of human malignant melanoma xenografts, RaH3 and RaH5, in nude mice is significantly inhibited by i.p. injections of 40 mg/kg/day canertinib (Fig. 4). The anti-proliferative effect on melanoma xenografts is visible already within 4 days of treatment and further increased throughout the treatment period as observed through the differences in tumor volumes, reaching statistical significance within 18 days of treatment^[2].