Synthesis of Small Molecule Inhibitors to Obstruct Inflammatory Cytokine Activity
Dr. Don L. Warner
We are interested in an inflammatory cytokine (IC) that is overexpressed in metastatic breast cancer, which is significant because there are more than 200,000 new cases of breast cancer diagnosed per year and it is expected to cause 42,690 deaths in 2020. The same IC is present in other inflammatory diseases such as systemic scleroderma, irritable bowel disease, and cystic fibrosis. The IC acts upon the JAK-STAT pathway, which causes gene transcription of inflammatory factors. Monoclonal antibodies which bind to the IC are in clinical trials but are an expensive solution. In order to find a more accessible treatment, small molecule inhibitors were screened computationally to bind to the IC. SMI-10 and SMI-26 showed successful binding through ELISA so we are using those as a base to synthesize novel compounds that bind with high affinity to the IC. By continually producing unique SMIs, we are simultaneously synthesizing potential drug candidates for treatment of diseases related to the IC as well as informing future SMI design. Ultimately, these binding studies will inform our drug design efforts to develop a cheaper, easily administered treatment for diseases caused by overexpression of the IC.
Fisch, Kyle; Day, Joey; Tuccinardi, Joseph; Olsen, Riley; and Warner, Don L., "Synthesis of Small Molecule Inhibitors to Obstruct Inflammatory Cytokine Activity" (2020). 2020 Undergraduate Research Showcase. 55.