BTK degrader UBX-303061

An orally bioavailable chimeric degrader of Bruton's tyrosine kinase (BTK) comprised of an E3 ubiquitin ligase ligand conjugated to a BTK-binding ligand, with potential antineoplastic activity. Upon oral administration, BTK degrader UBX-303061 specifically targets and binds, with its BTK-targeting moiety, to BTK and the E3 ubiquitin ligase ligand moiety 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 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.