Evaluation of the IRAK2 and IRAK3 pseudokinases as targets for novel drugs to treat inflammatory diseases

The innate immune system plays a critical role in producing compounds called cytokines that defend the body against infection by bacteria, viruses and other pathogens. However, the overproduction of some cytokines by the immune system is a major cause of inflammatory and autoimmune diseases that include arthritis, asthma, colitis, diabetes, lupus, psoriasis and sepsis. The Principal applicant has recently discovered that the production of these potentially harmful cytokines can be suppressed by switching off the function of a protein called IRAK2. The initial aims of the project are to work out the structure of IRAK2, and the function of a closely related molecule called IRAK3. This information will then be exploited to initiate the development of novel drugs to treat these diseases, which switch off IRAK2 and/or IRAK3 function and so reduce the levels of the harmful substances, called cytokines that trigger these conditions.