Roscovitine

Roscovitine, also known as seliciclib and CYC202, is a small molecule inhibitor of cyclin-dependent kinases (CDKs) that has been studied as a potential cancer therapy and as a research tool. It is commonly used to investigate the roles of CDKs in cell cycle control and transcription.

Roscovitine exhibits selective inhibition of several CDKs, most notably CDK2, CDK7, and CDK9, with weaker activity against others such as CDK1. By inhibiting CDK2, it can disrupt G1/S and S-phase progression; inhibition of CDK7 and CDK9 reduces phosphorylation of the RNA polymerase II C-terminal domain, thereby dampening transcription. This combination can promote cancer cell death in susceptible models while providing insight into basic CDK functions.

The compound acts as an ATP-competitive inhibitor, binding to the catalytic ATP-binding site of CDKs. Its potency and selectivity profile have made it a useful pharmacological tool but have also posed challenges for clinical development due to effects on normal proliferating cells and associated toxicities.

Clinical development has pursued roscovitine in several early-phase trials for various solid tumors and hematologic malignancies. While some anti-tumor activity has been observed in certain contexts, overall efficacy has been limited, and safety/tolerability concerns common to broad CDK inhibition have limited its progression as a cancer therapy. As a result, roscovitine has not been approved for cancer treatment and continues to be used mainly in preclinical and research settings.

Beyond oncology, roscovitine has been explored in preclinical models of neurodegenerative diseases and other conditions where modulation of transcription or cell cycle pathways may be relevant. It remains a widely used tool for studying CDK biology.