Imperial College London
Alternate

DrVassoTerzidou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Reader in Obstetrics and Gynaecology
 
 
 
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Contact

 

+44 (0)20 7594 2164v.terzidou

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pohl:2018:10.1124/jpet.118.247668,
author = {Pohl, O and Chollét, A and Kim, SH and Riaposova, L and Spézia, F and Gervais, F and Guillaume, P and Lluel, P and Méen, M and Lemaux, F and Terzidou, V and Bennett, PR and Gotteland, J},
doi = {10.1124/jpet.118.247668},
journal = {Journal of Pharmacology and Experimental Therapeutics},
title = {OBE022, an oral and selective prostaglandin F2α receptor antagonist as an effective and safe modality for the treatment of preterm labor},
url = {http://dx.doi.org/10.1124/jpet.118.247668},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Preterm birth is the major challenge in obstetrics affecting ~10% of pregnancies. Pan-prostaglandin synthesis inhibitors (NSAID) 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 and its parent OBE002, both potent and highly selective antagonist of the contractile PGF2α prostaglandin 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 to 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 PGF2α-induced human myometrial contractions alone and was more effective in combination with atosiban or nifedipine. In in vivo studies, OBE022 and OBE002 reduced spontaneous contractions in near-term pregnant rat. In pregnant mice, OBE022 delayed RU486-induced parturition and exerted synergistic effects in combination with nifedipine. OBE022 and/or OBE002 did not show the fetal side effects of ductus arteriosus constriction, impairment of kidney function or inhibition of platelet aggregation observed with indomethacin. Orally active OBE022 and OBE002 exhibits potent tocolytic effects on human tissues ex vivo and animal models in vivo without causing the adverse fetal side effects seen with indomethacin. Selectively targeting the FP receptor in combination with existing tocolytics may be an effective strategy for preventing or delaying preterm delivery.
AU  - Pohl,O
AU  - Chollét,A
AU  - Kim,SH
AU  - Riaposova,L
AU  - Spézia,F
AU  - Gervais,F
AU  - Guillaume,P
AU  - Lluel,P
AU  - Méen,M
AU  - Lemaux,F
AU  - Terzidou,V
AU  - Bennett,PR
AU  - Gotteland,J
DO  - 10.1124/jpet.118.247668
PY  - 2018///
SN  - 0022-3565
TI  - OBE022, an oral and selective prostaglandin F2α receptor antagonist as an effective and safe modality for the treatment of preterm labor
T2  - Journal of Pharmacology and Experimental Therapeutics
UR  - http://dx.doi.org/10.1124/jpet.118.247668
ER  -
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