BSJ-4-116 is a potent, CDK12 specific degrader (PROTAC) with IC50 of 6 nM, exhibits anti-proliferative activity in cancer cells.
BSJ-4-116 demonstrates a low nanomolar IC50 for inhibiting CDK12 enzymatic activity and exhibits potent CDK12 degradation in Jurkat cells in a dose- and time-dependent manner, while CDK13 protein level was minimally affected.
BSJ-4-116 also significantly suppresses the phosphorylation of Pol II Ser2 and Thr4, whereas p-Ser5 and p-Ser7 are not inhibited, and not affect the Cyclin K protein level.
BSJ-4-116 downregulates the expression of DDR genes and exhibits anti-proliferative activity in cancer cells.
BSJ-4-116 alone or in combination with PARP inhibitors could be a therapeutic avenue for targeting the intrinsic genomic instability inT-ALL model.
BSJ-4-116 overcomes resistance towards existing covalent inhibitors.
