BETd-246 (BETd246) is a potent, second-generation BET protein PROTAC degrader that exhibits superior selectivity, potency and antitumor activity.
BETd-246 completely and selectively depletes BRD2, BRD3 and BRD4 in representative TNBC cell lines with 30-100 nM for 1 h or with 10-30 nM for 3 h incubation.
BETd-246 displays strong growth inhibition and apoptosis induction activity in TNBC cell lines with IC50 <1 uM, induces a rapid and time-dependent downregulation of MCL1 protein.
BETd-246 decreases BET proteins in xenograft breast tumors and suppress tumor growth in vivo without causing weight loss.
