LZK-Targeting ATP-Competitive Catalytic Inhibitors Suppress LZK Catalytic Activity, Inhibit MYC Expression, Inhibit AKT Activation, and Promote Cancer Cell Death and Tumor Regression

Leucine Zipper-bearing Kinase (LZK) has been identified as a novel therapeutic target in squamous cell carcinomas with 50% of head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinomas (LSCC) patients showing amplifications or gains in LZK expression. Identifying successful therapies for the treatment of HNSCC or LSCC remains a significant unmet medical need.Researchers at the National Institutes of Health (NIH) have developed novel LZK-targeting ATP-competitive catalytic inhibitors as therapies for treating these two cancer subtypes. They have synthesized LZK-targeting inhibitors that suppresses LZK catalytic activity with micromolar affinity. The result is complete catalytic inhibition of the LZK kinase and suppression of kinase-dependent mechanisms of tumorigenesis. Specifically, these inhibitors suppress LZK kinase-dependent stabilization of MYC and activation of the PI3K/AKT pathway. LZK inhibitors promote almost complete cell death in cell line based models of HNSCC and significant levels of cell death in LSCC models.  The inventors welcome licensing and co-development interests to further develop and commercialize the technology.Inventors: John Brognard (NCI) Rolf Swenson (NCI)Commercial Advantages:LZK ATP-competitive catalytic inhibitors could serve as lead compounds for the development of new therapies for the treatment of LSCC and HNSCC and other cancers with amplified LZK that include prostate, ovarian and small cell lung ca...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Tags: Therapeutics Licensing Desired & Collaboration Desired Collaboration Sought NCI Source Type: research