C23 BTK-PROTAC

C23 BTK-PROTAC is a small molecule proteolysis-targeting chimera (PROTAC) designed to induce the degradation of Bruton tyrosine kinase (BTK). Developed for the treatment of mantle cell lymphoma (MCL), C23 is particularly effective against BTK variants that confer resistance to standard covalent and non-covalent BTK inhibitors, including the C481S and L528W mutations. In addition to BTK, C23 facilitates the degradation of the transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos), a dual-targeting mechanism shared with other clinical-stage degraders like NX-2127. This multi-target degradation leads to the suppression of B-cell receptor (BCR) signaling and downstream pathways such as NF-κB and PI3K-AKT-mTOR. Preclinical evidence demonstrates potent anti-proliferative activity in MCL cell lines and significant tumor growth inhibition in mouse xenograft models harboring resistant BTK variants.