Novel proteolysis targeting chimera (PROTAC) selectively targeting Leucine Zipper-bearing Kinase (LZK) limits oncogenic potential of head and neck cancers.

Head and neck squamous cell carcinomas (HNSCC) are aggressive epithelial tumors with a low and unchanged 50% 5-year survival rate. MAP3K13 gene encoding Leucine Zipper-bearing Kinase (LZK) is often amplified in HNSCC patients and can be an oncogenic driver for tumorigenesis. In order to reduce catalytic and non-catalytic functions of LZK we synthetized novel, potent and selective degrader of LZK protein using proteolysis targeting chimera technology. We confirmed efficiency and specificity of our PROTAC by Liquid chromatography-mass spectrometry analysis.