PROTAC BRD2/BRD4 degrader-1 (compound 15) serves as a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination of BRD4 and BRD2 compared to BRD3. Its efficacy in suppressing solid tumors manifest with minimal cytotoxic effects. This compound comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN)/cullin 4A[1].

PROTAC BRD2/BRD4 degrader-1 (100 nM; ≥8?hours) shows anti-proliferation activity with IC50 value of 12.25?nM, and the BRD4 protein is reduced very efficiently at treatment time of ≥8?h in MV4-11 cells[1]. PROTAC BRD2/BRD4 degrader-1 (100 nM; ≥8?hours) shows anti-proliferation activity with IC50 value of 12.25?nM, and the BRD4 protein is reduced very efficiently at treatment time of ≥8?h in MV4-11 cells[1]. PROTAC BRD2/BRD4 degrader-1 (1 nM, 3 nM, 0.1 μM, 0.3 μM; 24-48 hours) induces MV4-11 apoptosis lines[1]. PROTAC BRD2/BRD4 degrader-1 exhibits excellent anti-proliferative activity in 6 leukemia cell lines of NCI. Among them, the GI50 values of the three leukemia cell lines were lower than 50?nM, consistent with the activity of leukemia MV4-11 cells[1]. PROTAC BRD2/BRD4 degrader-1 has good anti-proliferation activity including prostate Cancer (22RV1 IC50: 0.081?μM), colon cancer (colo-205 IC50: 0.1557?μM) and thyroid cancer(TT IC50: 0.037451?μM)[1].