Bruton’s tyrosine kinase (Btk) plays a crucial role in B cell development and activation through the B cell receptor (BCR) signaling pathway and represents a new target for diseases characterized by inappropriate B cell activity[3]. AVL-292 is a highly selective, covalent Btk inhibitor with IC50 less than 0.5 nM. In Ramos cells which express an intact BCR signaling pathway, AVL-292 (0.1 nM-3 μM) potently inhibited Btk autophosphorylation on Tyr223 (EC50 = 8 nM), phosphorylation of the Btk substrate, PLCγ2, as well as activation of the downstream kinase. In the collagen-induced arthritis (CIA) model of arthritis, AVL-292 (3-30 mg/kg, p.o.) dose-dependently suppressed the clinical signs of inflammatory disease including reduction in joint and paw swelling and visible redness of the affected paws. Reduction of clinical signs of disease was measured at 95%, 85% and 50% for 30, 10 and 3mg/kg treatment respectively[3].
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