BT-O2C is a highly selective p300 PROTAC degrader that effectively reduces p300 levels in HAP1 cells. It exhibits significant cytotoxicity in CIC:DUX4 sarcoma (CDS) cell lines, with an IC50 of 152-221 nM, and notably decreases the expression of CDS target genes (ETV1, ETV4, ETV5). BT-O2C is applicable in cancer research.