HDAC3degrader-1 (Compound Z8) is a selective HDAC3 degrader with a DC50 of 2.42 µM. It shows minimal impact on HDAC1, HDAC2, and HDAC6. By inhibiting the activation of the NLRP3 inflammasome, HDAC3degrader-1 reduces the secretion of IL-1beta and caspase-1. It demonstrates significant efficacy in models of septic shock and colitis, making it valuable for anti-inflammatory research.