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Your search keyword '"Rix, Uwe"' showing total 5 results
Start Over Author "Rix, Uwe" Journal acs chemical biology
5 results on '"Rix, Uwe"'

1. Chemical Proteomics with Novel Fully Functionalized Fragments and Stringent Target Prioritization Identifies the Glutathione-Dependent Isomerase GSTZ1 as a Lung Cancer Target

Author

Liao, Yi, primary, Chin Chan, Sean, additional, Welsh, Eric A., additional, Fang, Bin, additional, Sun, Luxin, additional, Schönbrunn, Ernst, additional, Koomen, John M., additional, Duckett, Derek R., additional, Haura, Eric B., additional, Monastyrskyi, Andrii, additional, and Rix, Uwe, additional

Published
2023
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5. GSK3 Alpha and Beta Are New Functionally Relevant Targets of Tivantinib in Lung Cancer Cells

Author

Remsing Rix, Lily L., Kuenzi, Brent M., Luo, Yunting, Remily-Wood, Elizabeth, Kinose, Fumi, Wright, Gabriela, Li, Jiannong, Koomen, John M., Haura, Eric B., Lawrence, Harshani R., and Rix, Uwe

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 potency for GSK3α than for GSK3β and that pharmacological inhibition or simultaneous siRNA-mediated loss of GSK3α and GSK3β caused apoptosis. In summary, GSK3α and GSK3β are new kinase targets of tivantinib that play an important role in its cellular mechanism-of-action in NSCLC.

Published
2014
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