C23

C23 is an experimental proteolysis-targeting chimera (PROTAC) designed to target and degrade the Bruton's tyrosine kinase (BTK) protein. Developed primarily for the treatment of mantle cell lymphoma (MCL), C23 aims to overcome resistance associated with both covalent BTK inhibitors (such as ibrutinib) and non-covalent BTK inhibitors (such as pirtobrutinib). It achieves this by recruiting an E3 ubiquitin ligase to BTK, leading to its polyubiquitination and subsequent degradation by the 26S proteasome. Preclinical studies have demonstrated that C23 effectively degrades both wild-type BTK and mutant forms, including the C481S and L528W variants. By eliminating the BTK protein, C23 inhibits downstream signaling through the B-cell receptor (BCR), NF-κB, and PI3K-AKT-mTOR pathways, resulting in tumor cell apoptosis and suppressed proliferation in both in vitro and in vivo models.

Other names

BTK-PROTAC C23