Assay Development and Screening
Biochemical & Biophysical Assays
The second messenger cyclic dinucleotide (CDN) cGAMP is produced by the cGAS protein in response to activation by cytoplasmic dsDNA. Upon recognition of cGAMP by the stimulator of interferon genes (STING) protein, STING undergoes a substantial conformational change which leads to downstream upregulation of proinflammatory cytokines. Modulation of the cGAS/STING pathway is therefore considered a promising route for the treatment of inflammatory diseases as well as a potential partner for immune-oncology therapies. This presentation will describe the identification and optimization of compounds which were found to antagonize STING signaling as well as the identification and conformational characterization of non-CDN STING agonists.Techniques employed include surface plasmon resonance and X-ray crystallography.