HS-276, a potent and highly selective orally bioavailable transforming growth factor-β activated kinase-1 (TAK1) inhibitor with the Ki and IC50 of 2.5 nM and 2.3 nM respectively, shows significant inhibition of TNF-mediated cytokine profiles, correlating with significant attenuation of arthritic-like symptoms in the collagen-induced arthritis (CIA) mouse model of inflammatory rheumatoid arthritis (RA).