Enhanced Anti-Cancer Efficacy of BGB-11417: A Potent Bcl-2 Inhibitor for Hematological Tumors

The capacity to bypass cell death is a key feature of cancerous cells. The protein B-cell lymphoma-2 (Bcl-2), which prevents cell death, is often overly produced in various cancers, including lymphomas and leukemias, and can lead to the development of cancer or resistance to treatments. A drug called venetoclax, which targets Bcl-2, has been approved to treat a type of leukemia known as chronic lymphocytic leukemia (CLL). However, some patients with CLL have developed a mutation in Bcl-2 that makes venetoclax less effective.

Researchers have been studying a new drug, BGB-11417, which is a very strong and specific inhibitor of Bcl-2. In tests, BGB-11417 was able to effectively target both the normal and mutated forms of Bcl-2. It was found to be more effective than venetoclax in various tests, including binding to Bcl-2 and stopping the growth of cancer cells. BGB-11417 was particularly effective at stopping the growth of a type of leukemia cell line and was also able to kill a range of different cancer cells from lymphomas and leukemias.

The drug was also found to be very selective, meaning it targets Bcl-2 without affecting other similar proteins. In studies looking at how the drug is absorbed and works in the body, BGB-11417 showed a clear link between its concentration in the tumor and its ability to increase a marker of cell death. In addition, BGB-11417 was more effective than venetoclax in models of human leukemia and lymphomas without causing weight loss in the animals.

Overall, the research suggests that BGB-11417 is a powerful and selective Bcl-2 inhibitor with better anti-cancer effects than venetoclax in preclinical tests. A phase I study to evaluate BGB-11417 for treating blood cancers is currently underway.

The study was presented by Nan Hu and colleagues at the Annual Meeting of the American Association for Cancer Research in 2020.