459-Discovery of CARD9 Inhibitors for Anti-Inflammatory
This research article details the identification and development of small-molecule inhibitors targeting the CARD9 protein to treat inflammatory and autoimmune disorders. By leveraging human genetics, researchers discovered that while a total loss of CARD9 leads to immunodeficiency, partial loss-of-function variants provide protection against Crohn’s disease without compromising fungal immunity. Using DNA-encoded libraries and high-throughput screening, the team identified a benzodiazepine series that successfully disrupts CARD9 signaling and reduces the production of inflammatory cytokines…
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