GSK3 alpha and beta are new functionally relevant targets of tivantinib in lung cancer cells.

ABSTRACT: Tivantinib has been described as a potent and highly selective inhibitor of the receptor tyrosine kinase c-MET and is currently in advanced clinical development for several cancers including non-small cell lung cancer (NSCLC). However, recent studies suggest that tivantinib's anticancer properties are unrelated to c-MET inhibition. Consistently, in determining tivantinib's activity profile in a broad panel of NSCLC cell lines, we found that, in contrast to several more potent c-MET inhibitors, tivantinib reduces cell viability across most of these cell lines. Applying an unbiased, mass-spectrometry-based, chemical proteomics approach, we identified glycogen synthase kinase 3 (GSK3) alpha and beta as novel tivantinib targets. Subsequent validation showed that tivantinib displayed higher pot

SUBMITTER: Remsing Rix LL 

PROVIDER: S-EPMC3944088 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature