Drug candidate for neurological stroke and septic shock

Summary Apoptosis is a genetically regulated cellular suicide mechanism that plays an important role in regulating normal development and tissue homeostasis as well as pathogenesis of diseases. This process is mediated by one of at least 14 members of the Ced-3/ICE (caspase) family of cysteine proteases. Regulation of these activities may have therapeutic potential in the treatment of a wide range of diseases, from degenerative diseases such as Alzheimer's and Parkinson's to proliferative disorders such as lymphoma, p53-mediated carcinomas and autoimmune disorders. Caspase 11 is a member of this family. Until recently, it was not well characterized, and researchers did not understand its pathology. Caspase-11 is an upstream caspase which has been shown to be required for the activation of caspase-1 and for pro-IL-1b processing. While the expression of caspase-11 is undetectable in most tissues of healthy mice, it can be induced by a variety of pathological signals. Caspase-11-deficient mice showed a deficiency in processing pro-IL-1b as well as reduced number of apoptotic cells and a defect in caspase-3 activation. Harvard researchers have concluded that caspase-11 is involved in mediating cytokine secretion as well as apoptosis under brain ischemia and systemic inflammation. Harvard Medical School researchers in the laboratory of Dr. Junying Yuan have developed a cell based assay system that allowed them to screen for, and identify, inhibitors of Caspase 11 activity. Using this screen, they found an inhibitor of Caspase 11 expression that showed an IC50 of 50 uM. This drug lead was obtained from a natural source. The researchers subsequently developed a synthesis method to obtain more of the drug. The group is now synthesizing and testing analogues of the compound to develop preliminary structure activity data. Further work has shown that the molecule inhibits the NF-kappa B pathway and the STAT pathway that responds to interferon gamma

Applications Stroke Inflammation Septic shock For Further Information Please Contact the Director of Business Development Michal Preminger Email: [email protected] Telephone: (617) 432-0920

Inventor(s): Yuan, Junying

Type of Offer: Licensing



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