APG-3288

APG-3288 is a novel, next-generation Bruton's tyrosine kinase (BTK)-targeted protein degrader developed by Ascentage Pharma. It is a proteolysis-targeting chimera (PROTAC) molecule that functions by inducing the formation of a ternary complex between the BTK protein and the Cereblon (CRBN) E3 ubiquitin ligase. This recruitment leads to the polyubiquitination of BTK and its subsequent degradation by the 26S proteasome. Unlike traditional BTK inhibitors that only inhibit the kinase activity, APG-3288 eliminates the protein entirely, which allows it to overcome resistance mutations (such as C481S) that render conventional inhibitors ineffective. The drug is currently in Phase I clinical development for various relapsed or refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), and several subtypes of non-Hodgkin lymphoma.