BTRX-335140 (CYM-53093) is a potent and selective orally active κ-opioid receptor (KOR) antagonist with antagonistic activity against κOR, μOR, and δOR with IC50 values of 0.8, 110, and 6500 nM, respectively.

κ opioid receptor:0.8 nM, δ opioid receptor:6500 nM, μ opioid receptor:110 nM

METHODS: Tango OPRK1-bla U2OS cells were used to express KORs associated with the GAL4-VP16 transcription factor through the TEV protease locus.
RESULTS Navacaprant (BTRX-335140) showed antagonistic activity against κOR, μOR and δOR with IC50 values of 0.8 nM, 110 nM and 6.5 μM, respectively.[1]

METHODS: Mice were injected with BTRX-335140 (CYM-53093) (1 mg/kg, i.p.) 1 h and 24 h prior to the injection of U-50488 (15 mg/kg, i.v.) and tail-wagging latencies were measured at baseline, 30 min and 60 min after the agonist injection, while the mice were administered BTRX-335140 (CYM-53093) (3, 10, and 30 mg/kg) (3, 10, and 30 mg/kg) orally alone. 53093) (3, 10, and 30 mg/kg) alone, while mice were orally administered BTRX-335140 (CYM-53093) to assess the ability of BTRX-335140 (CYM-53093) to antagonize the antinociceptive effects of U-50488.
RESULTS BTRX-335140 (CYM-53093) (1 mg/kg, i.p.) blocked U-50488-induced antinociception within 1 h. The delayed tail-flash response induced by oral administration of BTRX-335140 (CYM-53093) (1 mg/kg) alone did not show any significant change in the tail-flash response induced by oral BTRX-335140 (CYM-53093) (1 mg/kg) at 1 h post-dosing in rats. 335140 (CYM-53093) (3, 10 and 30 mg/kg) also blocked U-50488-induced antinociception in a dose-dependent manner.