Discovery of a Highly Selective Tankyrase Inhibitor Displaying Growth Inhibition Effects against a Diverse Range of Tumor Derived Cell Lines

The
availability of high quality probes for specific protein targets
is fundamental to the investigation of their function and their validation
as therapeutic targets. We report the utilization of a dedicated chemoproteomic
assay platform combining affinity enrichment technology with high-resolution
protein mass spectrometry to the discovery of a novel nicotinamide
isoster, the tetrazoloquinoxaline 41, a highly potent
and selective tankyrase inhibitor. We also describe the use of 41 to investigate the biology of tankyrase, revealing the
compound induced growth inhibition of a number of tumor derived cell
lines, demonstrating the potential of tankyrase inhibitors in oncology.