Details

Project TitleMAP Kinase Targeted Therapeutics
Track Code2006-087
Short Description

A validated novel compound and medicinal chemistry refinement for bioavailable small molecule inhibitors of protein kinases or protein kinase-mediated cellular stress response pathways.

#therapeutics #cns

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. A platform for discovery and rapid refinement is established. An efficient synthetic scheme for the 069A lead p38α MAPK inhibitor and analogs has been developed. Current efforts focus on therapeutic index improvement in animal models and in vivo target validation.

 
TagsTHERAPEUTICS: CNS
 
Posted DateJul 3, 2011 11:09 AM

Inventor(s)

Linda J. Van Eldik

Daniel Martin Watterson*

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

IP Status

Issued US Patent No. 7,919,485

Contact Information

Gwendolyn Humphreys, PhD

Invention Associate 
(p) 847-467-0308
(e) Gwendolyn.Humphreys@northwestern.edu