MAP Kinase Targeted Therapeutics
- 技术优势
- High oral bioavailability Improved blood-brain barrier penetrance Increased metabolic stability Non-toxicity in rodent models Highly selective inhibition
- 详细技术说明
- 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
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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.
- *Inventors
- Linda J. Van Eldik Daniel Martin Watterson*
- *Publications
- Munoz L, Ranaivo HR, Roy SM, Hu W, Craft JM, McNamara LK, Chico LW, Van Eldik LJ and Watterson DM (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.
- 国家/地区
- 美国
