Pharmacologic characterization of CT-711, a novel dual inhibitor of ALK and c-Met.

ABSTRACT: Anaplastic lymphoma kinase (ALK) is a validated molecular target for patients harboring ALK rearrangement, which triggers the development of ALK inhibitors. However, the activation of mesenchymal-epithelial transition factor (c-Met) has emerged as a common cause of acquired resistance induced by selective ALK inhibitors. Herein, we report the first preclinical characterization of CT-711, a novel dual inhibitor of ALK and c-Met. CT-711 demonstrates potent inhibitory activity against ALK kinase activity. Moreover, CT-711 profoundly inhibits ALK signal transduction and thereby induces G1 phase arrest and apoptosis, and results in remarkable anti-proliferative activity against ALK-driven cancer cells. Furthermore, CT-711 effectively inhibits c-Met kinase activity and potently overcomes the res

SUBMITTER: Wang L 

PROVIDER: S-EPMC6129499 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature