Clinical Drug Experience Knowledgebase

BN-82451 belongs to a family of small molecules designated as multitargeting or hybrid molecules. BN-82451 is orally active, has good central nervous system penetration, and elicits potent neuronal protection and antiinflammatory properties. BN-82451 acts via three major pathways involved in neuronal death: excito-toxicity, oxidative stress, and inflammation, and is also a mitochondrial protective agent. Because BN-82451 is a multitargeting agent, each of its specific sites of action has been extensively evaluated, namely, neuronal excitotoxicity (sodium channel blocker), oxida-tive stress (antioxidant), neuroinflammation (cyclooxygenase inhibitor), and mitochondrialdysfunction (mitochondria-protective properties). BN-82451 was found to exert a significant protection in experimental animal models mimicking aspects of cerebral ischemia, Parkinson disease, Huntington disease, and more particularly amyotrophic lateral sclerosis. BN-82451 is in phase II clinical trials by Ipsen Pharma for the treatment of Huntington’s disease. In 2015, orphan drug designation was assigned in the U.S. to the compound for the indication.   ^NCATS