Atrimers for autoimmune disorders / Bird Rock Bio, Mitsubishi Tanabe 
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  • ||||||||||  Atrimers for autoimmune disorders / Bird Rock Bio, Mitsubishi Tanabe
    Journal:  Dissecting Programmed Cell Death with Small Molecules. (Pubmed Central) -  Apr 7, 2021   
    Furthermore, we developed a biomimetic synthetic strategy based on diverse Diels-Alder reactions in the total syntheses of ainsliadimers A and B, ainsliatrimers A and B, and gonchnatiolides A-C, which are natural product inhibitors or activators for PCD...In addition, TQ-ligation has been applied in the discovery of heat shock protein 90 (HSP90) as one of the functional target proteins for kongensin A. We also confirmed that kongensin A covalently attaches to Cys420 within HSP90 and demonstrated that kongensin A blocks the interaction between HSP90 and CDC37 and subsequently inhibits necroptosis. Our development of these diverse PCD modulators provides not only effective chemical tools for fundamental biomedical research, but also the foundation for drug discovery targeting important human diseases such as cancers and inflammation caused by malfunction of PCD.