AC0676

AC0676 is an investigational, orally bioavailable small molecule chimeric degrader of Bruton's tyrosine kinase (BTK), developed by Accutar Biotechnology for the treatment of relapsed or refractory B-cell malignancies. It functions as a proteolysis-targeting chimera (PROTAC), utilizing an E3 ubiquitin ligase ligand conjugated to a BTK-binding ligand to induce selective degradation of both wildtype and mutant forms of BTK—including C481S and L528W mutants—via the ubiquitin-proteasome system. By degrading BTK rather than merely inhibiting its kinase activity, AC0676 removes both the kinase and scaffolding functions of BTK, potentially overcoming resistance mechanisms seen with covalent and non-covalent BTK inhibitors. Preclinical studies have demonstrated potent anti-tumor activity in animal models. As of 2023–2025, it is in Phase 1 clinical trials for various B-cell malignancies including non-Hodgkin lymphoma subtypes and chronic lymphocytic leukemia[1][2][4][5][7].

Other names

BTK degrader AC0676