Success of Prostaglandin E2 in Structure–Function Is a Challenge for Structure-Based Therapeutics
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OBE022, an Oral and Selective Prostaglandin F2α Receptor Antagonist As an Effective and Safe Modality for the Treatment of Pret
Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2018/05/18/jpet.118.247668.DC1 1521-0103/366/2/349–364$35.00 https://doi.org/10.1124/jpet.118.247668 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 366:349–364, August 2018 Copyright ª 2018 by The American Society for Pharmacology and Experimental Therapeutics OBE022, an Oral and Selective Prostaglandin F2a Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor s Oliver Pohl, André Chollet, Sung Hye Kim, Lucia Riaposova, François Spézia, Frédéric Gervais, Philippe Guillaume, Philippe Lluel, Murielle Méen, Frédérique Lemaux, Vasso Terzidou, Phillip R. Bennett, and Jean-Pierre Gotteland ObsEva SA, Plan-les-Ouates, Geneva, Switzerland (O.P., A.C., J.-P.G.); Imperial College London, Parturition Research Group, Institute of Reproductive and Developmental Biology,HammersmithHospitalCampus,EastActon,London,UnitedKingdom(S.H.K.,L.R., V.T., P.R.B.); Citoxlab, Evreux, France (F.S., F.G.); Porsolt Research Laboratory, Le Genest-Saint-Isle, France (P.G.); Urosphere SAS, Toulouse, France (P.L., M.M.); BioTrial, Rennes, France (F.L.); and André Chollet Consulting, Tannay, Switzerland (A.C.) Downloaded from Received February 26, 2018; accepted May 15, 2018 ABSTRACT Preterm birth is the major challenge in obstetrics, affecting aggregation. In in vitro studies, OBE002 inhibited sponta- ∼ 10% of pregnancies. Pan-prostaglandin synthesis inhibitors neous, oxytocin- and PGF2a-induced human myometrial jpet.aspetjournals.org [nonsteroidal anti-inflammatory drugs (NSAIDs)] prevent preterm contractions alone and was more effective in combination labor and prolong pregnancy but raise concerns about fetal renal with atosiban or nifedipine. -
Effect of Latanoprost Or 8-Iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes
LABORATORY SCIENCES Effect of Latanoprost or 8-iso Prostaglandin E2 Alone and in Combination on Intraocular Pressure in Glaucomatous Monkey Eyes Rong-Fang Wang, MD; Steven M. Podos, MD; Janet B. Serle, MD; Thomas W. Mittag, PhD; F. Ventosa, MD; Bernard Becker, MD Objective: To evaluate the possible additivity of the ef- duction of IOP of 4.0 ± 0.6 mm Hg was produced when fects of latanoprost and 8-iso prostaglandin E2 (8-iso PGE2) 8-iso PGE2 was added to latanoprost and of 3.0 ± 0.7 on intraocular pressure (IOP) in monkey eyes with laser- mm Hg was produced when latanoprost was added to 8-iso induced glaucoma. PGE2 on day 13 before the morning dosing. Combina- tion therapy with both agents caused maximum IOP re- Methods: The IOP was measured hourly for 6 hours be- ductions from baseline of 11.3 ± 3.0 mm Hg (33%) (P,.05) ginning at 9:30 AM on day 1 (baseline day), days 6 and 7 (latanoprost with 8-iso PGE2 added) and of 9.8 ± 1.3 , (single-agent therapy), and days 13 and 14 (combination mm Hg (31%) (P .01) (8-iso PGE2 with latanoprost added) therapy with both agents). Following 1 day of baseline mea- on day 14. surement, 4 monkeys with unilateral glaucoma received monotherapy twice daily with either 1 drop of 0.005% la- Conclusion: Latanoprost and 8-iso PGE2 have an addi- tanoprost, or 0.1% 8-iso PGE2, 25 µL, at 9:30 AM and 3:30 tive effect on IOP in glaucomatous monkey eyes. -
Effects of Prostaglandin F2α (Pgf2α) on Cell-Death Pathways in the Bovine Corpus Luteum
Jonczyk et al. BMC Veterinary Research (2019) 15:416 https://doi.org/10.1186/s12917-019-2167-3 RESEARCH ARTICLE Open Access Effects of prostaglandin F2α (PGF2α) on cell- death pathways in the bovine corpus luteum (CL) Agnieszka Walentyna Jonczyk, Katarzyna Karolina Piotrowska-Tomala* and Dariusz Jan Skarzynski Abstract Background: Prostaglandin F2α (PGF2α) may differentially affect viability of luteal cells by inducing either proliferation or cell death (via apoptosis or necroptosis). The diverse effects of PGF2α may depend on its local vs. systemic actions. In our study, we determined changes in expression of genes related to: (i) apoptosis: caspase (CASP) 3, CASP8, BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and (ii) necroptosis: receptor-interacting protein kinase (RIPK) 1, RIPK3, cylindromatosis (CYLD), and mixed lineage kinase domain-like (MLKL) in the early and mid-stage corpus luteum (CL) that accompany local (intra-CL) vs. systemic (i.m.) analogue of PGF2α (aPGF2α) actions. Cows at day 4 (n = 24) or day 10 (n = 24) of the estrous cycle were treated by injections as follows: (1) systemic saline, (2) systemic aPGF2α (25 mg; Dinoprost), (3) local saline, (4) local aPGF2α (2.5 mg; Dinoprost). After 4 h, CLs were collected by ovariectomy. Expression levels of mRNA and protein were investigated by RT-q PCR, Western blotting and immunohistochemistry, respectively. Results: We found that local and systemic administration of aPGF2α in the early-stage CL resulted in decreased expression of CASP3 (P < 0.01), but CASP8 mRNA expression was up-regulated (P < 0.05). However, the expression of CASP3 was up-regulated after local aPGF2α treatment in the middle-stage CL, whereas systemic aPGF2α administration increased both CASP3 and CASP8 expression (P < 0.01). -
Misoprostol Induces Relaxation of Human Corpus Cavernosum Smooth Muscle: Comparison to Prostaglandin E1
International Journal of Impotence Research (2000) 12, 107±110 ß 2000 Macmillan Publishers Ltd All rights reserved 0955-9930/00 $15.00 www.nature.com/ijir Misoprostol induces relaxation of human corpus cavernosum smooth muscle: comparison to prostaglandin E1 RB Moreland1, NN Kim1, A Nehra2, BG Parulkar3 and A Traish1,4* 1Department of Urology, Boston University School of Medicine, Boston, MA 02118, USA; 2Department of Urology, Mayo Clinic and Foundation, Rochester, MN 55905, USA; 3Department of Urology, University of Massachusetts Medical Center, Worcester, MA 01604, USA; and 4Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA Prostaglandin E1 (PGE1) relaxes trabecular smooth muscle by interacting with speci®c G-protein coupled receptors on human corpus cavernosum smooth muscle and increasing intracellular synthesis of cAMP. Misoprostol (CytotecTM), is an oral prostaglandin E analogue. The purpose of this study was to compare the functional activity of misoprostol with PGE1 in human corpus cavernosum and cultured human corpus cavernosum smooth muscle cells. Misoprostol, misoprostol free acid or PGE1 induced dose-dependent relaxations in strips of human corpus cavernosum. At concentrations greater than 1076 M, tissue recontraction was observed with all three agents. This was abrogated by pretreatment with the thromboxane A2 receptor antagonist SQ29,548. From these observations, we conclude that misoprostol is activated by human corpus cavernosum in situ and relaxes phenylephrine-precontrated tissue -
Adverse Periocular Reactions to Five Types of Prostaglandin Analogs
Eye (2012) 26, 1465–1472 & 2012 Macmillan Publishers Limited All rights reserved 0950-222X/12 www.nature.com/eye 1 1 1 1 Adverse periocular K Inoue , M Shiokawa , R Higa , M Sugahara , CLINICAL STUDY T Soga1, M Wakakura1 and G Tomita2 reactions to five types of prostaglandin analogs Abstract Purpose We investigated the appearance explained to patients before PG frequency of eyelid pigmentation and administration. eyelash bristles after the use of five types of Eye (2012) 26, 1465–1472; doi:10.1038/eye.2012.195; prostaglandin (PG) analogs. published online 5 October 2012 Methods This study included 250 eyes from 250 patients diagnosed with primary open- Keywords: prostaglandin analogs; adverse angle glaucoma or ocular hypertension who reactions; eyelid pigmentation; eyelash bristles; were treated with either latanoprost, patient’s subjective evaluation; physician’s travoprost, tafluprost, bimatoprost, or subjective evaluation isopropyl unoprostone for 43 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by Introduction three ophthalmologists who were masked to treatment type. The existence of eyelid Prostaglandin (PG) analogs are the primary pigmentation and eyelash bristles was treatment for glaucoma because of their judged, and images of the left and right eyes powerful intraocular pressure (IOP) decreasing were compared. Subjective symptoms effect, few systematic adverse reactions, and regarding the existence of eyelid convenience of once a day administration (other pigmentation and eyelash bristles were than isopropyl unoprostone (unoprostone)).1 Five types of PG analogs (latanoprost, investigated through a questionnaire. 1Inouye Eye Hospital, Tokyo, Results There was no significant difference travoprost, tafluprost, bimatoprost, and Japan between the five types of medications with unoprostone) are currently available in Japan. -
Tafluprost: the First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension
See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/232647942 Tafluprost: The First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension Article in Annals of Pharmacotherapy · October 2012 DOI: 10.1345/aph.1R229 · Source: PubMed CITATIONS READS 13 154 2 authors, including: Michael Neville Wingate University School of Pharmacy 11 PUBLICATIONS 87 CITATIONS SEE PROFILE All content following this page was uploaded by Michael Neville on 21 November 2014. The user has requested enhancement of the downloaded file. ARTICLES New Drug Approvals Tafluprost: The First Preservative-Free Prostaglandin to Treat Open-Angle Glaucoma and Ocular Hypertension Cory Swymer and Michael W Neville afluprost 0.0015% ophthalmic solu- tion (Zioptan) was approved by the T OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical trial data, Food and Drug Administration on Febru- efficacy data, and adverse effect incidence of tafluprost. ary 10, 2012, for the treatment of elevated DATA SOURCES: A literature search was completed using PubMed, Web of intraocular pressure (IOP) in patients with Science, and Google Scholar. Tafluprost was the primary search term. Articles open-angle glaucoma, in addition to ocular published between January 2008 and April 2012 were included in this review. hypertension.1 Although it has been used Additional limits placed on the searches were “human” and “English.” Citations in in other countries since 2008, tafluprost is which tafluprost appeared in the title were 36, 29, and more than 300 in PubMed, Web of Science, and Google Scholar, respectively. the first preservative-free prostaglandin STUDY SELECTION AND DATA EXTRACTION: Three clinical trials were included in analogue commercially available in the this review. -
Travatan, INN-Travoprost
SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of Travatan. This scientific discussion has been updated until 1 November 2003. For information on changes after this date please refer to module 8B. 1. Introduction Travoprost is a prostaglandin analogue intended for use to reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. The product is presented in a concentration of 40 µg/ml of preserved eye drops (0.004%). The dose is one drop of Travoprost Eye Drops in the conjunctival sac of the affected eye(s) once daily. Travoprost Eye Drops contains travoprost (AL- 6221), a prostaglandin analogue, in a sterile ophthalmic solution formulation and it is a selective, full agonist for the FP prostanoid receptor. FP receptor agonists are reported to reduce IOP by increasing uveoscleral outflow. Rationale for the product Glaucoma is the leading cause of irreversible blindness in the world. It is a frequent disease and it has been estimated that 66.8 million have glaucoma, 6.7 million of whom are bilaterally blind. Open angle glaucoma is the most common type, mainly primary but also, in some cases, open angle glaucoma is secondary to the exfoliation syndrome or other primary ocular diseases. Glaucoma is an optic neuropathy that leads to loss of optic-nerve tissue with an excavation of the ophthalmoscopically visible optic nerve head and consequently, to a progressive loss of vision. The elevated IOP is the main risk factor for its development and reduction of IOP has been demonstrated to protect against further damage to the optic nerve, even in patients with IOP that is statistically "normal" (so called normal tension glaucoma). -
Summary of Product Characteristics
SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT [Invented name] 0.3 mg/mL + 5 mg/mL eye drops, solution 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One mL of solution contains 0.3 mg of bimatoprost and 5 mg of timolol (as 6.8 mg of timolol maleate). Excipient with known effect One mL of solution contains 0.95 mg phosphates. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Eye drops, solution Clear, colorless, aqueous solution, practically free from particles pH: 6.8-7.8 Osmolality: 290 mOsm/Kg ± 10 % (261-319 mOsm/Kg) 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Reduction of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues. 4.2 Posology and method of administration Posology Recommended dose in adults (including older people) The recommended dose is one drop of [Invented name] in the affected eye(s) once daily, administered either in the morning or in the evening. It should be administered at the same time each day. Existing literature data for preservative-containing bimatoprost/timolol 0.3 mg/mL + 5 mg/mL eye drops, solution suggest that evening dosing may be more effective in IOP lowering than morning dosing. However, consideration should be given to the likelihood of compliance when considering either morning or evening dosing (see section 5.1). If one dose is missed, treatment should continue with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily. -
Bimatoprost 0.03%/Timolol 0.5% Preservative-Free Ophthalmic
BJO Online First, published on March 25, 2014 as 10.1136/bjophthalmol-2013-304064 Clinical science Br J Ophthalmol: first published as 10.1136/bjophthalmol-2013-304064 on 25 March 2014. Downloaded from Bimatoprost 0.03%/timolol 0.5% preservative-free ophthalmic solution versus bimatoprost 0.03%/timolol 0.5% ophthalmic solution (Ganfort) for glaucoma or ocular hypertension: a 12-week randomised controlled trial Ivan Goldberg,1 Rafael Gil Pina,2 Aitor Lanzagorta-Aresti,3 Rhett M Schiffman,4 Charlie Liu,4 Marina Bejanian4 ▸ Additional material is ABSTRACT As topical medications are normally dispensed published online only. To view Aim To compare the efficacy and safety of single-dose from multiuse bottles, preservative (typically ben- please visit the journal online (http://dx.doi.org/10.1136/ bimatoprost 0.03%/timolol 0.5% preservative-free (PF) zalkonium chloride, BAK) is employed to maintain bjophthalmol-2013-304064). ophthalmic solution with bimatoprost 0.03%/timolol sterility. Although many patients use preservative- 0.5% ophthalmic solution in patients with open-angle containing medications without adverse effects,10 11 1Department of Ophthalmology, University of glaucoma or ocular hypertension. some become sensitive to ophthalmic preserva- 12 13 Sydney, Sydney Eye Hospital, Methods In this multicentre, randomised, parallel- tives. A single-dose, preservative-free (PF) oph- Sydney, Australia group study, patients were randomised to bimatoprost/ thalmic fixed combination would benefit this patient 2 Clinica Oftalmologica Rafael timolol -
Oral Titrated Misoprostol for Induction of Labor: Anmc
4/16/21njm ORAL TITRATED MISOPROSTOL FOR INDUCTION OF LABOR: ANMC BACKGROUND The incidence of labor induction has been steadily rising, and the rate of induced labor currently ap- proaches 25 per cent, owing to the large number of referred patients with a medical indication for delivery, principally postdates pregnancy, hypertensive disease of pregnancy, and other maternal and fetal condi- tions necessitating delivery. Induction of labor can be a long and tedious process and involves considera- ble resource expenditure. The incidence of cesarean delivery is increased following induced labor, partly due to the risk condition for which the procedure was undertaken, and partly due to a lack of cervical “ripeness” or readiness for labor. The Bishop score is a reasonable clinical guide that references the cer- vical shortening, softening, and dilation that takes place as pregnancy advances. Bishop scores of 5 or less are considered unfavorable, and are inversely related to the success of the induction and the length of labor. Both mechanical (Foley balloon, Atad balloon, Cook catheter system, seaweed based dilators) and phar- macologic methods (oxytocin and various prostaglandins, including misoprostol (Cytotec), dinoprostone (Cervidil) have been used to ripen the unfavorable cervix. Review of the current evidence suggests that the prostaglandin misoprostol, administered either orally or intravaginally, are generally considered the more effective agent for cervical ripening and induction of labor. This drug has a good safety profile at the lower dosage range, and is convenient to use, but there are limitations to its use, particularly in women with a uterus previously scarred as a result of cesarean delivery. -
PGD2/DP2 Receptor Activation Promotes Severe Viral Bronchiolitis by Suppressing IFN- Λ Production Cheryl A
of wheezing and infantile colic in the first year of life. This compared with those from healthy subjects. RSV- association appears to be stronger with increasing antibi- infected cultured human primary airway epithelial otic duration. There was a trend toward allergic sensiti- cells also revealed increased PGD2 production. In a zation in infants who were treated with antibiotics. No neonatal mouse model of severe viral bronchiolitis, significant association was found with regard to the de- DP2 antagonism decreased viral load, promoted antiviral velopment of eczema. immunity, and ameliorated type 2 inflammation and bronchiolitis. This protective effect was replicated REVIEWER COMMENTS. The authors of this study demonstrate with a specific DP1 agonist and lost with DP1/DP2 that neonatal antibiotic administration may predispose antagonism. children to wheezing and colic. The authors of past studies have linked early-life antibiotics (not limited to CONCLUSIONS. The authors conclude that PGD2 contributes the neonatal period) with wheezing but report a link to disease severity by suppressing antiviral immunity and fl between antibiotic exposure and infantile colic. Further promoting type 2 in ammation. DP2 blockade or DP1 studies are needed to determine if these findings are agonism increased interferon-I expression and viral due to the alteration of gut microbiota during a critical clearance. Thus, DP2 antagonists or DP1 agonists may window. Optimization of indications for starting be a useful treatment of viral bronchiolitis and a antibiotics, early discontinuation if possible, and the possible preventive for asthma and other diseases with administration of probiotics may be indicated. pathogeneses related to viruses. REVIEWER COMMENTS. The authors of this study highlight the URL: www.pediatrics.org/cgi/doi/10.1542/peds.2018–2420RRR importance of PGD2 during RSV bronchiolitis and suggest Shazia Lutfeali, MD a similar role in the development of asthma after an RSV Christopher Parrish, MD infection. -
Long-Term Effectiveness and Safety of Tafluprost, Travoprost, And
Journal of Clinical Medicine Article Long-Term Effectiveness and Safety of Tafluprost, Travoprost, and Latanoprost in Korean Patients with Primary Open-Angle Glaucoma or Normal-Tension Glaucoma: A Multicenter Retrospective Cohort Study (LOTUS Study) Joon-Mo Kim 1 , Kyung-Rim Sung 2, Hwang-Ki Kim 3, Sang-Woo Park 4, Eun-Ji Lee 5, Jin-Wook Jeoung 6 , Hae-Young Lopilly Park 7, Jaehong Ahn 8, Chungkwon Yoo 9 and Chan-Yun Kim 10,* 1 Department of Ophthalmology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Korea; [email protected] 2 Department of Ophthalmology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul 05505, Korea; [email protected] 3 Department of Ophthalmology, Kim’s Eye Hospital, Myung-Gok Eye Research Institute, Konyang University, Seoul 07301, Korea; [email protected] 4 Department of Ophthalmology and Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju 61469, Korea; [email protected] 5 Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea; [email protected] Citation: Kim, J.-M.; Sung, K.-R.; 6 Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Kim, H.-K.; Park, S.-W.; Lee, E.-J.; Hospital, Seoul 03080, Korea; [email protected] Jeoung, J.-W.; Park, H.-Y.L.; Ahn, J.; 7 Department of Ophthalmology, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Yoo, C.;