BSJ-03-204 is a PROTAC (proteolysis targeting chimera) [1
]. It is a hybrid molecule that simultaneously inhibits CDK4/CDK6 kinase activity and recruits E3 ligase CRL4CRBN
to target these kinases for destruction via
E3 ligase-mediated ubiquitination and proteasomal degradation. The CDK4/CDK6 inhibitor palbociclib
is linked to an imide-based cereblon ligand via
a linker molecule. BSJ-03-204 has an oxylamide in place of the thalidomide aryl amine nitrogen, and this blocks degradation of IKZF1 and IKZF3 (which are known targets of imides and some imide‐based degraders).