Ebopiprant

Ebopiprant (OBE022) is an oral and selective prostaglandin F_2α (PGF_2α) receptor antagonist, with K_is of 1 nM, 26 nM for human and rat FP receptors, respectively. IC50 & Target: Ki: 1 nM (human FP receptors), 26 nM (rat FP receptor)^[1]. In Vitro: Ebopiprant (OBE022) and OBE002 are assayed for FP binding affinity by competitive binding analysis with 3H-PGF2α using HEK293 cells stably transfected with the FP receptor. Binding affinities (K_i) of OBE022 for the human and rat FP receptor are 1 nM and 26 nM respectively. For OBE002, K_is are 6 nM for the human and 313 nM for the rat FP receptor. The binding of both OBE022 and OBE002 is reversible and competitive since increasing concentrations of either compound causes successive decreases in the slope of the binding curves, consistent with an increase in equilibrium dissociation constant (K_D) without a reduction in receptor density^[1]. In Vivo: Time-course of the cumulative percentage of delivers mice after RU486-induced preterm parturition at GD17, in OBE022, nifedipine or vehicle treatment groups. Oral treatment with OBE022 delays the preterm birth caused by RU486 administration as reflected by a shift to the right of the percentage of delivery curve. The effect of oral treatment with nifedipine is comparable. Both OBE022 and nifedipine show a trend to increase the time of first pup delivery. As an important consequence of the prolongation of gestation, dams deliver viable pups. Combination of OBE022 and nifedipine cause a synergistic effect on the delay of RU486-induced preterm birth as reflected by a more pronounced shift to the right of the percentage of delivery curve, in comparison to OBE022 or nifedipine alone. Also, a larger increase of the time of first pup delivery is observed^[1].