Y-320

Abstract: The invention discloses application of an immunomodulator Y-320 as an antitumor chemotherapeutic drug-resistant sensitizer, and an antitumor drug composition. The antitumor drug composition comprisesan antitumor chemotherapeutic drug and a sensitizer, The sensitizer is the immunomodulator Y-320. Found by researches, Y-320 is combined with anti-tumor drugs such as paclitaxel, vinorelbine and doxorubicin by a drug medium to prepare a novel anti-tumor combination drug and effectively kill tumor cells. Y-320 is a sensitizer or a drug-resistant reversal agent of an antitumor drug, tumors includingliver cancer, pancreatic cancer, cholangiocarcinoma, breast cancer and the like. New ways and means are provided for effective treatment of tumors.

Abstract: Interleukin (IL)-15 and IL-17 are thought to play an important role in the pathogenesis of rheumatoid arthritis (RA) because both pro-inflammatory cytokines are found in synovial fluid of RA patients. In this study, we examined the pharmacological profiles of Y-320, a new phenylpyrazoleanilide immunomodulator. Y-320 inhibited IL-17 production by CD4 T cells stimulated with IL-15 with IC50 values of 20 to 60 nM. Oral administration of Y-320 (0.3 to 3 mg/kg) significantly inhibited the development and progression of arthritis and joint destruction with reduction of IL-17 mRNA expression in arthritic joints of type II collagen-induced arthritis (CIA) in DBA/1J mice. Y-320 in combination with anti-murine tumor necrosis factor-α monoclonal antibody showed a synergistic effect on mouse CIA. Moreover, therapeutic treatment with Y-320 (0.3 and 1 mg/kg orally) ameliorated CIA in cynomolgus monkeys. Our results suggest that Y-320, an orally active inhibitor for IL-17 production, provides a useful therapy for RA.