BPI-1178 is a high effective and selective self-developed cyclin-dependent kinase (CDKs)4/6 inhibitor , which is intended to treat hormone receptor positive (HR)/ human epidermal growth factor receptor 2 negative (HER2) breast cancer and other solid tumors. CDK4/6 is activated after binding to cyclin D, which can promote the phosphorylation of retinoblastoma protein (Rb) and play a key role in the signal pathway of cell cycle progression and cell proliferation. However, CDK4/6 inhibitors can inhibit Rb phosphorylation, prevent the progression of G1 to S phase of cell cycle, and thus inhibit the proliferation of tumor cells. Based on its mechanism of action, CDK4/6 inhibitors have become one of the important targets of anti-tumor therapy.
BPI-1178 is an oral CDK4/6 inhibitor, which has a very similar molecular structure with the similar drugs Palbociclib, Ribociclib and Abemaciclib. BPI-1178 is an innovative targeted inhibitor based on the same core structure, developed after optimized design and screening. The results of non-clinical studies, such as molecular level and cell level trials, a number of pharmacodynamics, toxicological evaluation and pharmacokinetic trials of xenograft nude mouse models, show that BPI-1178 is a safe and effective CDK4/6 inhibitor with remarkable anti-tumor effect. BPI-1178 has very favorable DMPK properties, and it can penetrate the blood-brain barrier. It showed BPI-1178 monotherapy or combination therapy inhibited xenograft tumor growth of human breast cancer, lung cancer and glioblastoma. IND Approval is received from NMPA in 2019 November.
Inhibition of CDK4/6 blocks phosphorylation of the human retinoblastoma protein (Rb), resulting in G1 cell cycle arrest and a shutdown of cell proliferation. Pre-clinical studies showed outstanding anti-cancer activities against breast cancer, lung cancer, and glioblastoma. Animal studies showed BPI-1178 could effectively penetrate through the blood-brain barrier.