HDAC6 degrader-5 (Compound 6) exhibits inhibitory and degradation activity against HDAC6 , with an IC 50 of 4.95 nM and a DC 50 of 0.96 nM. HDAC6 degrader-5 inhibits the release of TNF-α, IL-1β and IL-6 , blocks the hepatocyte apoptosis. HDAC6 degrader-5 exhibits anti-inflammatory activity in mouse APAP -induced liver injury models.