Design, synthesis and anti-tumor activity of BTK inhibitor Orelabrutinib derivatives.

Summary: Scientists are constantly looking for better ways to fight cancer. In this study, researchers focused on a protein called BTK, which plays a key role in the growth of certain blood cancers. Using an existing drug called Orelabrutinib as a blueprint, they analyzed exactly how it locks onto the BTK protein. With this knowledge, they used a technique called "scaffold hopping"—essentially tweaking the chemical structure to create new variations—to design 28 new compounds. After testing these new versions in the lab, they found two specific compounds, named 11a and 11k, were highly effective at stopping tumor cells from growing and spreading. These findings offer a promising starting point for developing potent new cancer treatments.