Small Molecule Inhibitors of Costimulatory Protein-Protein Interactions
Peter Buchwald, Emilio Margolles-Clark, Norma Kenyon and Camillo Ricordi
Problem
Protein-protein interactions are important in a number of biological processes that lead to disease. By interfering with these interactions, detrimental health conditions such as autoimmune diseases, neurodegenerative disorders, transplant rejection, and graft-versus-host disease may be prevented. The development of therapeutic compounds however, has been limited, as there are no well-defined drug binding pockets that are traditional targets for drugs to bind to.
Solution
A group of small molecule inhibitors for CD40/CD154 protein-protein interactions has been identified. Because of their structure, they appear to interfere and prevent the interactions from occurring. These small molecules are azo dyes and related compounds, many of which are known to bind to certain proteins and can be used for staining and visualization of cells and cellular processes. The molecules are more effective in preventing the interactions than other compounds that are currently known, and there is accumulating evidence that selectivity for the protein-protein interaction of interest might be achievable with some of them.
Competitive Advantage
The development of compounds that interfere with protein-protein interactions is an emerging field, as traditional approaches for drug development are ineffective. A novel drug discovery tool has been developed by using azo dye related small molecules as a scaffold.
Applications
The invention can be used as a convenient starting point for novel drug discovery, as an active structural scaffold has been identified.
Patent Status
International Patent Application No. PCT/US2009/042831 was filed on May 5, 2009.
Licensing Opportunity
We are seeking commercialization partnerships for the use of organic dye related small molecules as a novel drug development tool.
About the Inventors
Peter Buchwald, Ph.D. is an Assistant Professor at the Department of Molecular and Cellular Pharmacology and the Director of the Drug Discovery Program at the Diabetes Research Institute (DRI) at the University of Miami Leonard M. Miller School of Medicine. He has worked in multi-disciplinary fields related to drug design and development both in the academic and industrial settings.
Emilio Margolles-Clark, Ph.D., is an Assistant Scientist in Translational Research at the DRI.
Norma Kenyon, Ph.D., is the Martin Kleiman Professor of Surgery, Medicine, Microbiology and Immunology and Director of the Wallace H. Coulter Center for Translational Research at the University of Miami. In addition, she serves as the Associate Director of Research and Program Development and Director of Pre-Clinical Islet Transplantation at the DRI.
Camillo Ricordi, M.D., holds the Stacy Joy Goodman Chair and serves as Distinguished Professor of Medicine and Professor of Surgery, Biomedical Engineering, Microbiology and Immunology. Dr. Ricordi is also Chief of the Division of Cellular Transplantation, Department of Surgery and the Scientific Director and Chief Academic Officer of the DRI.
Selected References
Kenyon, N. S.; Chatzipetrou, M.; Masetti , M.; Ranuncoli, A.; Oliveira, M.; Wagner, J. L.; Kirk , A. D.; Harlan, D. M.; Burkly, L. C.; Ricordi , C. Long-term survival and function of intrahepatic islet allografts in rhesus monkeys treated with humanized anti-CD154. Proc. Natl. Acad. Sci. U.S.A., 1999, 96, 8132-8137.
