105963-46-0

TOK-8801 is a synthesized dihydroimidazothiazole carboxamide and is under development as an immunomodulator. TOK-8801 augments the in vitro anti-SRBC PFC response of murine splenocytes in a bell-shaped manner. The stimulatory effect of TOK-8801 is observed at concentrations of 2.5×10 ^-7 to 2.5×10 ^-5 M and is diminished at 10 ^-4 M. The cell-viability is not altered during the culture with TOK-8801 at any doses used in this experiment (10 ^-7 to 10 ^-4 M). TOK-8801 enhances the ³ H-TdR uptake of these responses in a bell-shaped manner, and effective concentrations of TOK-8801 are 10 ^-7 to 10 ^-5 M.

The anti-SRBC PFC response per spleen, which is prominently lowered by restraint-stress (P<0.05), is significantly restored by the administration of TOK-8801 (0.5 mg/kg, P<0.05). The number of total splenic lymphocytes in restraint-stress is decreased, but there are no significant changes in the number of total splenic lymphocytes by the treatment with TOK-8801. When TOK-8801 is administered orally at doses of 0.1 to 10 mg/kg, the number of plaque forming cell (PFC) significantly decreases or tends to decrease. Treatment of TOK-8801 at doses of 0.1 to 1 mg/kg causes significant suppression in the delayed-type hypersensitivity (DTH) reaction induced in high responder.