Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits

We report the development of a novel, aqueous-soluble, safe, small molecule, experimental therapeutic that suppresses injury-induced, proinflammatory cytokine increases in the brain, with resultant attenuation of synaptic protein biomarker loss and improvement in hippocampus-dependent behavioral deficits. A GMP production scheme for the active pharmaceutical ingredient, compound 17, is presented. The development and large-scale availability of this novel compound allow exploration of new, potentially disease-modifying, therapeutic approaches to CNS disorders.

Graphical abstractDevelopment of an orally bioavailable, water-soluble, stable, safe, anti-neuroinflammatory compound with in vivo efficacy in altering disease progression in a neurodegenerative disease animal model is reported.Figure optionsDownload full-size imageDownload as PowerPoint slide