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The natural immune system uses a series of pattern recognition receptors (PRRs) to monitor extracellular danger signals, non-self components of the cytoplasm, and self-injury-related molecules to initiate an immune response
Recently, Zhang Ao's research team from the School of Pharmacy of Shanghai Jiaotong University and Tang Wei's research team from Shanghai Institute of Materia Medica have obtained results in the study of small molecule inhibitors for targeted cGAS treatment of inflammation and autoimmune diseases related to cGAS-STING pathway dysfunction Progress, the work was published in J.
In response to the weak cell activity of most of the existing cGAS inhibitors, the team synthesized two series of small molecule inhibitors I and II based on the structural characteristics of cGAS, using bio-electronic isosteric, side chain extension and other pharmaceutical strategies; and Using the framework migration strategy, the C9-substituted aryl group was changed and moved to the C12-position to synthesize series III and IV; then further intramolecular rearrangement or cyclization on the basis of IV, respectively, to obtain series V and VI (Figure 1)
