Since the 'pre-replicative complex' of ORC, Cdc6, RLF-B/Cdt1 and Mcm2-7 are involved in recruiting both Xic1 (through Cdc6 and cyclin E/Cdk2) and SCF (through Mcm2–7), this provides a mechanism ...

Because of flexibility, the disruption of the p27 Kip1 –cyclin A–Cdk2 complex can proceed in a step-wise, segmental fashion, which likely provides a kinetic advantage for the overall process.

"These striking new findings validate the combination of INX-315 with CDK4/6 inhibitors as a promising therapeutic strategy with potential application beyond patients with CDK2-addicted cancers ...

The dual mechanism of action results in deep and durable ... platform to induce previously unexplored interactions within the CDK2 ATP binding pocket, leading to increased potency and selectivity ...