TYD-68 is a highly efficient and selective CRBN-recruited TYK2 PROTAC degrader with a DC50 value of 0.42 nM. TYD-68 significantly inhibits IL-12 and IFN-α-induced STAT4 and STAT1 phosphorylation, thereby blocking TYK2-dependent signaling pathways. TYD-68 can be used in the study of psoriasis. (Pink: Target protein ligand ; Black: Linker (HY-W007732B) ; Blue: E3 ligase ligand (HY-14658) ; E3 ligase ligand + Linker (HY-173358) ).