Dual BCL-xL/BCL-2 degrader 753b (Compound 753b) is a highly potent dual BCL-xL and BCL-2 PROTAC degrader with DC50 of 6 nM and 48 nM for degrading BCL-xL and BCL-2 in 293T cells respectively.
Dual BCL-xL/BCL-2 degrader 753b (Compound 753b) is a highly potent dual BCL-xL and BCL-2PROTAC degrader with DC50 of 6 nM and 48 nM for degrading BCL-xL and BCL-2 in 293T cells respectively.
753b is a better PROTAC than DT2216 to induce the formation of the ternary complex.
753b degrades BCL-xL and BCL-2 in a VHL- and proteasome-dependent manner.
753b could substantially degrade WT and K20- and K87-only BCL-xL mutants, but not K16-only BCL-xL mutant.
753b is more potent than DT2216, ABT199 (a selective BCL-2 inhibitor) and ABT263 in killing Kasumi-1 cells by induction of apoptosis.
753b (5 mg/kg every four days) induced tumor regressions in H146 xenograft models.
