OBE022, an Oral and Selective Prostaglandin F2α Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor

The Journal of Pharmacology and Experimental Therapeutics
Oliver PohlJean-Pierre Gotteland

Abstract

Preterm birth is the major challenge in obstetrics, affecting ∼10% of pregnancies. Pan-prostaglandin synthesis inhibitors [nonsteroidal anti-inflammatory drugs (NSAIDs)] prevent preterm labor and prolong pregnancy but raise concerns about fetal renal and cardiovascular safety. We conducted preclinical studies examining the tocolytic effect and fetal safety of the oral prodrug candidate OBE022 [(S)-2-amino-3-methyl-butyric acid (S)-3-{[(S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carbonyl]-amino}-3-(4-fluoro-phenyl)-propyl ester] and its parent OBE002 [(S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carboxylic acid [(S)-1-(4-fluoro-phenyl)-3-hydroxy-propyl]-amide], both potent and highly selective antagonist of the contractile prostaglandin F2 α (PGF2 α ) receptor (FP). Efficacy of OBE022 and OBE002, alone and in combination with other tocolytics, was assessed in human tissues and pregnant animal models for inhibition of uterine contraction and delay of parturition. Selective safety of OBE022 and/or OBE002, compared with NSAID indomethacin, was assessed on renal function, closure of the ductus arteriosus, and inhibition of platelet aggregation. In in vitro studies, OBE002 inhibited spontaneous, oxytocin- and PGF2 α -induced human my...Continue Reading

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Citations

Apr 2, 2019·Current Pharmaceutical Design·Ronald F Lamont, Jan S Jørgensen
Sep 14, 2019·Endocrinology·Masahide YoshidaKatsuhiko Nishimori
Apr 26, 2020·The Journal of Perinatal & Neonatal Nursing·Lindsey Garfield, Emily Chin
Sep 25, 2020·Journal of Cell Communication and Signaling·Roger G Biringer
Jan 29, 2019·Therapeutic Innovation & Regulatory Science·Simon CoatesUlrike Lorch
Feb 9, 2021·Cytokine & Growth Factor Reviews·Elizabeth PrairieSylvain Chemtob

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