Definition

An orally bioavailable, central nervous system (CNS)-penetrating, irreversible covalent inhibitor of Bruton’s tyrosine kinase (BTK), with potential antineoplastic activity. Upon oral administration, BTK inhibitor GB5121 selectively targets, irriversibly binds to and inhibits the activity 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. GB5121 is able to penetrate the blood-brain-barrier (BBB) and may thereby treat BTK-driven CNS tumors and metastasis.