Research & Development
Seliciclib is a novel, orally-available inhibitor of CDK2/E, CDK2/A, CDK7 and CDK9 - enzymes that are central to the process of cell division and cell cycle control and play pivotal roles in cancer cell growth and DNA damage repair. Inhibition of CDKs 2 and 9 may also correct aberrant cell cycle control in certain non-malignant diseases of proliferation. Seliciclib exerts an anti-proliferative effect via several key mechanisms:
- selective downregulation of proliferative and survival proteins and upregulation of p53, leading to growth arrest or apoptosis;
- decreasing phosphorylation of Rb and modulating E2F transcriptional activity leading to growth arrest or apoptosis;
- inhibiting HR and NHEJ DNA repair pathways, resulting in synergy with DNA damaging agents; and
- in sequence with chemotherapy, overcoming cell cycle related drug resistance.
Seliciclib has been evaluated in 16 clinical trials and administered to over 450 subjects including healthy volunteers. It is sparing to the bone marrow as observations of myelosuppression are rare.