Research & Development
CYC065 – Second Generation CDK Inhibitor
CYC065 is a highly-selective, orally-available, 2nd generation inhibitor of cyclin dependent kinases (CDK) 2, 5 and 9. These CDK enzymes play pivotal roles in cancer cell growth, metastatic spread and DNA damage repair. Pharmacological inhibition of CDK2 and CDK9 has been shown to have potent anticancer effects in certain tumor types resistant to established treatments. CYC065 causes apoptotic cell death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Translational biology supports the development of CYC065 as a stratified medicine for solid tumors as well as orphan diseases including adult and pediatric leukemias. Published preclinical studies show that CYC065 has the potential for development in acute myeloid leukemia, chronic lymphocytic leukemia and drug-resistant breast cancer.
CYC065 is mechanistically similar to Cyclacel's first generation CDK inhibitor, seliciclib, but with significantly improved potency in vitro and in vivo. CYC065 causes proportionally greater CDK9 inhibition, leading to improved efficacy in hematological malignancies and more prolonged down regulation of MCL1. CYC065 has improved metabolic stability compared with seliciclib and shows improved efficacy and dose potency. CYC065 is in a Phase 1 study of patients with solid tumors with potential utility in both hematological malignancies and solid tumors.
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