While screening a library of compounds synthesized in our laboratory against a panel of tumor cell lines, we came across a series of 2-benzylidene-4H-benzo<b>[1,4]thiazin-3-one compounds that preferentially kill the cancer cells and spare the normal cells in cytotoxicity assay. To understand the mechanism of cytotoxicity of these compounds, we selected one of the active molecules 108110 from this library and screened against a panel of 355 functional recombinant kinases in in vitro and it found to be a very potent inhibitor of CK2 and PIM3 kinases. Casein kinase 2 (CK2) and Pim kinases (Pim-1, 2 and 3) are a class of serine/threonine kinases that are highly homologous in their kinase domains and have been implicated in several normal biological process including cell survival, proliferation, differentiation and apoptosis. It is well known that constitutive activation or over expression of these kinases also results in cellular transformation and tumorigenesis. Consequently, 108110 as an inhibitor of these kinases may be a promising candidate for drug development against the cancers where these kinases are involved. Here in we describe the synthesis, characterization, structure activity relationship (SAR), cytotoxicity, kinase profile and CK2 protein bound crystal structure of ON 108110.

ON 108110, a novel kinase inhibitor: Description of the synthesis, kinase profiling, and co-crystal structure

245th National Meeting (2013)

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