CDK inhibitor 24 is a potent inhibitor of cyclin-dependent kinases (CDKs) with IC50 of 4/20/64 nM for CDK2/9/12, respectively.
CDK inhibitor 24 causes dephosphorylation of retinoblastoma protein and RNA polymerase II, leading to induction of apoptosis in cellular assays in lymphoma cell lines.
CDK inhibitor 24 also induces proteasome-dependent degradation of cyclin K both in vitro and in a patient-derived xenograft in vivo.
CDK inhibitor 24 has a dual mechanism of action, acting as a CDK inhibitor and as a molecular glue inducing an interaction between CDK12 and DDB1 that leads to polyubiquitination of cyclin K and its subsequent degradation.
