Early Phase I Data on an Irreversible Pan-Er Inhibitor: CI-1033. What Did We Learn?

Abstract

CI-1033 (Canertinib dihydrochloride) is an orally available pan-erbB receptor tyrosine kinase inhibitor that, unlike the majority of receptor inhibitors, effectively blocks signal transduction through all four members of the erbB family. In addition, it blocks the highly tumorigenic, constitutively activated variant of erbB-1, EGFRvIII, and inhibits downstream signaling through both the Ras/ MAP kinase, and PI-3 kinase/AKT pathways (Figure 1). CI-1033 is also unique in that it is an irreversible inhibitor; thereby providing prolonged suppression of erbB receptormediated signaling. Preclinical data show CI-1033 to be efficacious against a variety of human tumors in mouse xenograft models, including breast carcinomas.

Keywords:

• CI-1033
• canertinib dihydrochloride
• pan-erbB receptor tyrosine kinase inhibitor