Inhibitors of Interleukin-15 (IL-15) Receptor
IL-15 is an important cytokine for the immune system. IL-15 binds to its receptor and the activation of IL-15 receptor is essential for inflammation and immune response. IL-15 stimulates T cell proliferation. In addition, IL-15 is required for the development, survival, and activation of natural killer (NK) cells, homeostasis of natural killer T (NKT) cells, and maintenance of memory CD8+ T cells.
Using an on-bead two-color (OBTC) combinatorial cell-screening technology, we discovered a new compound that is able to bind and completely inhibit the function of IL-15 receptor at 10 μM concentration. The compound is named SPSA3Q1. It is a peptoid (oligo-N-substituted glycine) which closely resembles peptide except that the side chain extends from the main chain nitrogen rather than from the α-carbon. It is protease-resistant and highly tissue permeable, and is non-immunogenic.
We are in the process of optimizing the structure of SPSA3Q1 and hope to develop more potent derivatives of the compound. These inhibitors of IL-15 receptor have potential to become drugs that
have wide range of clinical applications. For example, IL-15 plays an important role in rheumatoid arthritis, a disease that affects millions and is difficult to treat. Blocking IL-15 is able to prevent arthritis in mice, indicating a potential use of these compounds in the treatment of arthritis. In addition, these compounds may be used to treat autoimmune diseases and other diseases involving inflammation: inflammatory bowel disease (IBD, ulcerative colitis and Crohn disease); multiple sclerosis; and prevention of rejection during organ transplantation. Peptoids are economical to synthesize and optimize.
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Bin Guo
Associate Professor, Department of Pharmacological & Pharmaceutical Sciences