Definition

An orally bioavailable reversible inhibitor of Bruton’s tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon oral administration, BTK inhibitor TT-01488 non-covalently binds to and inhibits the activity of BTK, including the C481S mutated form, a resistance mutation in the BTK active site in which cysteine is substituted for serine at residue 481. This prevents the activation of the B-cell antigen receptor (BCR) signaling pathway 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 the development, activation, signaling, proliferation and survival of B lymphocytes. BTK C481S mutation plays an important role in resistance to certain BTK inhibitors.