MAP Kinase Targeted Therapeutics

NU 2006-087

 

Inventors

Linda J. Van Eldik

Daniel Martin Watterson*

 

Abstract

Northwestern researchers have identified and validated a novel compound with significant potential in the treatment of neurological diseases. In addition to the specific compound, this invention includes medicinal chemistry refinement which improves the bioavailability of small molecular inhibitors of protein kinases or protein kinase-medicated cellular stress response pathways. The investigators identified a small molecule p38α MAPK inhibitor which presents great therapy potential for CNS disorders in which proinflammatory cytokine overproduction is a component, such as Alzheimers (AD) and related indications, Parkinson's, multiple sclerosis, and traumatic brain injury. The CNS kinase inhibitor features a number of significant characteristics, making it an ideal candidate for CNS therapy. These include improved molecular properties having good oral bioavailability, blood-brain barrier penetrance, metabolic stability, and non-toxicity in in vivo rodent models. Furthermore, the inhibitor exhibited significant in vitro inhibition selectivity for only the p38α MAPK isoform.

 

Applications

  • Therapeutics: Small Molecule for CNS

 

Advantages

  • High oral bioavailability
  • Improved blood-brain barrier penetrance
  • Increased metabolic stability
  • Non-toxicity in rodent models
  • Highly selective inhibition

 

Publications

Munoz L, Ranaivo H, Roy S, Hu W, Craft J, McNamara L, Chico L, Van Eldik L and Watterson D (2007) A novel p38α MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model. Journal of Neuroinflammation. 4: 21.

 

IP Status

Issued US Patent No. 7,919,485

Patent Information: