Palbociclib and derivatives. (A) Palbociclib and derivative compounds with differences in kinase inhibition due to modest changes to the piperazine-linker tail. (B) Several PROTAC candidates using various linkers and either a von Hippel-Lindau (VHL)- or a cereblon-recruiting ligand. (C) YX-2-107, a CRBN-palbociclib PROTAC, selectively degrades CDK6 in BV173 cells after 4 hours of treatment. (D) Synthesis of CRBN E3-amine component for cereblon E3 ligase recruitment and as a control.