Definition

An orally bioavailable, targeted degrader of Bruton’s tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase) comprised of an E3 ubiquitin ligase binding moiety conjugated, via a linker, to a BTK-binding moiety, with potential antineoplastic activity. Upon oral administration of BTK degrader ABBV-101, the BTK-targeting moiety targets and binds to BTK, and the E3 ligase-binding moiety targets and binds to E3 ubiquitin ligase. This catalyzes ubiquitination and proteasome-mediated degradation of BTK, and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B-lymphocyte development, activation, signaling, proliferation and survival.