MT-802 (MT802) is a potent BTK PROTAC degrader that induces degradation of both wild-type and C481S mutant BTK (DC50=9.1 nM).
MT-802 recruits BTK to the cereblon E3 ubiquitin ligase complex to trigger BTK ubiquitination and degradation via the proteasome.
MT-802 binds fewer off-target kinases than ibrutinib does and retains an equivalent potency (>99% degradation at nanomolar concentrations) against wild-type and C481S BTK, elicits complete BTK knockdown at 250 nM。
MT-802 reduces the pool of active, phosphorylated BTK in cells isolated from CLL patients with the C481S mutation, whereas ibrutinib cannot.
