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

Summary
The National Cancer Institute (NCI) seeks research co-development partners and/or licensees for Leucine Zipper-bearing Kinase (LZK)-targeting ATP-competitive catalytic inhibitors and LZK-targeting proteolysis-targeting chimeras (PROTACs) as a therapeutic for treating cancers that over-express LZK , such as head and neck, lung and ovarian squamous cell carcinoma, as well as small cell lung cancers.
NIH Reference Number
E-169-2021
Product Type
Keywords
  • Leucine Zipper-bearing Kinase, LZK, MAP3K13, Proteolysis-targeting Chimera, ATP-Competitive Catalytic Inhibitors, Degraders, Head and Neck Squamous Cell Carcinoma, HNSCC, Amplified oncogenes, Ovarian cancer, Small Cell Lung Cancer, LSCC, VHL Warhead, Brog
Collaboration Opportunity
This invention is available for licensing and co-development.
Contact
Description of Technology

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.

Potential Commercial Applications
  • 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 cancer. 
  • The aim is to develop these inhibitors in the near term and develop a lead compound for the treatment of HNSCC patients.

 

Competitive Advantages
  • 50% of HNSCC and LSCC patients have amplifications or gains in LZK
  • ATP-competitive catalytic inhibitors specifically targeting LZK and have preferred drug-like characteristics 
  • Could be licensed in combination with LZK-targeting PROTACs

 

 

Inventor(s)

John Brognard Ph.D. (NCI), Rolf Swenson Ph.D (NCI)

Development Stage
Publications
  • Funk A, et al. LZK inhibition suppresses HNSCC tumor growth via c-MYC and mutant p53. (To be submitted)

 

Patent Status
  • U.S. Provisional: U.S. Provisional Patent Application Number 63/239,797, Filed 01 Sep 2021
Therapeutic Area
Posted
Wednesday, November 3, 2021