JHD205, A Novel Abemaciclib Derivative, Exerts Antitumor Effects on Breast Cancer by CDK4/6

aims: compound JHD205 is an effective breast cancer treatment and offers patients a new targeted therapy option. background: Triple-negative breast cancer (TNBC) is an aggressive, difficult-to-treat cancer subtype with a poor prognosis and an urgent need for effective targeted molecular therapies. objective: By inhibiting the phosphorylation of the retinoblastoma protein (Rb), selective CDK4/6 inhibitors can induce cell cycle G1 phase hindrance, potentially making them effective therapeutic options for TNBC. method: The compound JHD205 was synthesized based on the chemical structure of Abemaciclib, which inhibits the malignant phenotype of TNBC cells. result: Breast cancer xenograft chicken embryo models showed better tumor growth inhibition with compound JHD205 versus Abemaciclib. Meanwhile, western blot analysis showed that compound JHD205 could degrade CDK4 and CDK6 in a dose-dependent manner, while other proteins related to CDK4/6, such as p-Rb, Rb and E2F1, showed abnormal changes. Furthermore, the compound JHD205 induces apoptosis, DNA damage, and inhibits DNA repair by upregulate CASPASE 3 and p-H2AX protein levels. conclusion: As a result, compound JHD205 is a potential therapeutic strategy for the treatment of breast cancer. other: none