ONO-4059 analog is the [(3S)-1-(1-oxo-2-propen-1-yl)-3-piperidinyl] analog of the recently published structure of ONO-4059. ONO-4059 is an orally bioavailable inhibitor of Bruton’s tyrosine kinase (BTK; IC50 = 2.2 nM), a non-receptor tyrosine kinase involved in signal transduction pathways regulating the proliferation, activation, and differentiation of B cells. ONO-4059 reversibly blocks B cell receptor signaling and B cell proliferation and activation. ONO-4059 suppresses the generation of inflammatory chemokines and cytokines in a mouse model of collagen-induced arthritis, resulting in regression of cartilage erosion, bone damage, and pannus formation. ONO-4059 is in clinical trials concerning certain leukemias and lymphomas, including chronic lymphocytic leukemia. The actions of ONO-4059 analog have not been studied.
