Selective CDK6 degradation mediated by cereblon, VHL, and novel IAP-recruiting PROTACs.

We report here the preparation of palbociclib-based PROTACs that incorporate binders for three different E3 ligases, including a novel IAP-binder, which effectively degrade CDK4 and CDK6 in cells. In addition, we show that the palbociclib-based PROTACs in this study that recruit different E3 ligases all exhibit preferential CDK6 vs. CDK4 degradation selectivity despite employing a selection of linkers between the target binder and the E3 ligase binder.
PMID: 32184044 [PubMed - as supplied by publisher]

Source: Bioorganic and Medicinal Chemistry Letters - March 9, 2020 Category: Chemistry Authors: Anderson NA, Cryan J, Ahmed A, Dai H, McGonagle GA, Rozier C, Benowitz AB Tags: Bioorg Med Chem Lett Source Type: research