PROTAC EZH2 Degrader-9 is orally active EZH2 PROTAC degrader degrading EZH2 via the ubiquitin-proteasome pathway. PROTAC EZH2 Degrader-9 downregulates PRC2 core subunits and potent inhibition of H3K27me3 without affecting common CRBN neosubstrates while it was selective over GSp'T1 and ikZF1/3. PROTAC EZH2 Degrader-9 exhibits potent antiproliferative activity against multiple cancer cell lines by inducing cell cycle and apoptosis. PROTAC EZH2 Degrader-9 reverses PRC2-mediated gene silencing and inhibiting EZH2 non-catalytic target gene activation. PROTAC EZH2 Degrader-9 can be used for leukemia, lymphoma, and non-small cell lung cancer research.
(Pink: EZH2 ligand ; Blue: Cereblon ligand ; Black: linker).
