Fig. 3. In vivo activity of the discovered EP4R antagonist.

“n” denotes number of independent animals. a Carrageenan-mediated mechanical allodynia (von Frey test) is reduced by systemic administration of EP4R antagonists. 77 exhibits significant anti-allodynic properties through i.p. (n = 5) or oral (p.o., n = 10) administration of 30 mg/kg of the molecule. b CJ-42794 and 77 equally reduce carrageenan-mediated mechanical allodynia (von Frey test) upon i.p. injections of 10 mg/kg (n = 10 per group). c Pre-treatment with 10 or 30 mg/kg 77 by i.p. administration (n = 5), 30 minutes prior to intraplantar PGE₂ injection, dose-dependently reduces mechanical allodynia (von Frey test). d CFA-induced mechanical allodynia (von Frey test) is reduced by i.p. administration of 10 (n = 5) and 30 mg/kg (n = 5) of 74 after three and four days. e Carrageenan-induced paw edema was reduced upon i.p. administration of 30 mg/kg 77 (n = 10 per cohort). f Injections of 77 on four consecutive days significantly reduced the progression of CFA-induced inflammation (n = 5 per cohort). p-values between indicated groups in a)-d) were calculated with two-tailed unpaired t-tests. p-values in e) and f) were calculated with multiple unpaired two-tailed t-tests at each timepoint. In a)-f) data is shown as mean ± SEM. Source data are provided as a Source Data file.