Description

Y-320 is an orally active immunomodulator, and inhibits IL-17 production by CD4 T cells stimulated with IL-15 with IC50 of 20 to 60 nM.

In vitro

Y-320 also inhibits the production of IFN-γ and TNF-α by mouse CD4 T cells stimulated with IL-15, CXCL12, and anti-CD3 mAb.

In vivo

Y-320 (0.3-3 mg/kg p.o.) ameliorates collagen-induced arthritis (CIA) in Mice with a reduction of IL-17 mRNA in arthritic joints, and also shows therapeutic effects on CIA in cynomolgus monkeys. Moreover, Y-320 shows a synergistic effect in combination with anti-TNF-α mAb on chronic-progressing CIA in mice.

Uses

1-(4-Chlorophenyl)-N-(3-cyano-4-(4-morpholinopiperidin-1-yl)phenyl)-5-methyl-1H-pyrazole-4-carboxamide inhibits T cell activation induced by IL-15 and shows a therapeutic effect on collagen-induced arthritis in DBA/1J mice.

Biological Activity

y-320 is a new phenylpyrazoleanilide immunomodulator [1].immunotherapy refers to treatment of disease by suppressing, inducing or enhancing an immune response.y-320 is a new phenylpyrazoleanilide immunomodulator. y-320 inhibited il-17 production by cd4 t cells induced by il-15 with ic50 values of 20-60 nm [1].in type ii collagen-induced arthritis (cia) mice, oral administration of y-320 (0.3-3 mg/kg) reduced il-17 mrna expression and significantly inhibited the development of joint destruction and arthritis. the combination of y-320 with anti-murine tumor necrosis factor-α (tnf-α) monoclonal antibody exhibited a synergistic effect. in cynomolgus monkeys, y-320 (0.3-1 mg/kg) relieved cia. these results suggested that y-320 could be a useful candidate for therapy of rheumatoid arthritis (ra) [1].

in vivo

IC 50

IL-15; IL-17

References

[1]. ushio h, ishibuchi s, oshita k, et al. a new phenylpyrazoleanilide, y-320, inhibits interleukin 17 production and ameliorates collagen-induced arthritis in mice and cynomolgus monkeys. pharmaceuticals (basel), 2013, 7(1): 1-17.