Esonarimod (KE-298), a derivative of propionic acid developed in Japan, has been shown to suppress various animal models of arthritis by inhibiting the production of inflammatory cytokines, such as IL-1β, IL-6 and IL-8, from human peripheral blood mononuclear cells. In vitro, the two stereoisomers showed equivalent potency for antagonism of interleukin-1 and enhancement of lymphocyte transformation. Esonarimod also inhibited tumour necrosis factor-α-induced proliferation of synovial cells. Inhibition of proliferation of cells was not due to nonspecific cytotoxicity. Treatment with esonarimod also significantly reduced chloramphenicol acetyltransferase activity in synovial cells, and diminished activity of the transcription factor AP-1 in the nucleus of synovial fibroblast-like cells. In a phase II trial among 60 patients with rheumatoid arthritis, esonarimod 100-200 mg/day PO for 12 weeks produced significant improvements in the Lansbury index.