Identification of protein substrates of a novel proteolysis targeting chimera, PROTAC124 in tongue squamous cell carcinoma cell line CAL-33 overexpressing Leucine Zipper-bearing Kinase (LZK).

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 shotgun proteomic analysis.