Ferring Research Institute Inc.
Ferring Research Institute Inc.
Sonesson A.,Ferring Pharmaceuticals A S |
Koechling W.,Non Clinical Development |
Stalewski J.,Ferring Research Institute Inc. |
Tanko L.B.,Clinical RandD |
Rasmussen B.B.,Ferring Pharmaceuticals A S
Drug Metabolism and Disposition | Year: 2011
Degarelix is a novel competitive gonadotropin-releasing hormone receptor blocker (antagonist). In this study, the nonclinical metabolism and excretion of degarelix was investigated in Sprague-Dawley rat, beagle dog, and cynomolgus monkey. Degarelix was found to be stable when incubated in microsomes and cryopreserved hepatocytes from animal liver tissue. Absorption, distribution, metabolism, and excretion studies in male rat, dog, and monkey showed that after a subcutaneous dose of tritium-labeled degarelix, the peptide was rapidly absorbed with C max in plasma of 1 to 2 h. The predominant route of excretion was via the kidneys and the bile. In rat and dog, most of the degarelix dose was eliminated within 48 h via urine and feces in equal amounts (40-50% in each matrix), whereas in monkey the major route of excretion was fecal (50%) and renal (22%). In plasma and urine samples from all three species, mainly intact degarelix was detected. In bile and feces samples from rats and dogs, the same truncated peptides of the parent decapeptide were detected. The major metabolites identified represented the N-terminal tetrapeptide, the pentapeptide, and the heptapeptide. From the animal studies, it could be concluded that degarelix is subject to common peptidic degradation in the liver and bile and is fully excreted via metabolic and biliary (as metabolites and parent compound) and urinary (mainly as parent compound) pathways. Systemic exposure to metabolic products seems to be low. Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics.
Danese S.,University of Milan |
Schabel E.,Federal Institute for Drugs and Medical Devices |
Masure J.,Ferring Research Institute Inc. |
Plevy S.,Janssen Research & Development |
Schreiber S.,University of Kiel
Journal of Crohn's & colitis | Year: 2016
The role of placebo in clinical trials for drug development in inflammatory bowel disease [IBD] was the topic of a panel discussion held during the 10th Congress of the European Crohn's and Colitis Organisation [ECCO], in Barcelona, Spain, in 2015. Panellists discussed a number of issues around placebo-controlled trials in IBD, noting issues such as difficulties with recruitment, leading to less then representative patient populations in clinical studies. It was noted that, whereas the easiest answer may be to drop placebo, it is much more complicated than that. The relevance of placebo is affected by a number of factors, including the phase of the trial, as well as the nature of the drug. In most cases where placebo has been left out in drug development, it has been for trials involving a new formulation, a new dosing schedule, or a biosimilar, for example. The panel agreed that placebo-controlled trials are of particular importance early in the development programme, perhaps not so much in phase III, although placebo is important for monitoring safety. The current trial paradigm, in which patients remain on a plethora of, likely ineffective and toxic, background medication, was also questioned. The applicability of placebo in the paediatric population was also discussed. The overall consensus from this panel discussion was that placebo is still necessary in clinical trials in inflammatory bowel disease, but there remain questions as to how and when placebo should be used. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Sueiras-Diaz J.,Ferring Research Institute Inc. |
Zhang Y.,Ferring Research Institute Inc. |
Velentza A.,Ferring Research Institute Inc. |
Santoso B.,Ferring Research Institute Inc. |
Yang S.,Ferring Research Institute Inc.
Tetrahedron Letters | Year: 2017
We report herein, for the first time, a sequential total chemical synthesis of the Human Growth Hormone analog [Nle14,125,170,Glu29,91,Gln74,Asn107,Asp109]hGH-NH2, composed of a 191 amino acid residue polypeptide chain containing two disulfide bonds and nine modifications in the natural sequence. Sequential native chemical ligation of three discrete segments of 52, 52 and 87 amino acid residues gave the target full-length polypeptide chain. Subsequent folding with concomitant formation of the native disulfide bonds afforded a correctly folded homogeneous analog which is biologically active. © 2017 The Authors
Lau J.L.,Ferring Research Institute Inc. |
Dunn M.K.,Ferring Research Institute Inc.
Bioorganic and Medicinal Chemistry | Year: 2017
Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts. We maintain a comprehensive dataset on peptides that have entered human clinical studies that includes over 150 peptides in active development today. Here we provide an overview of the peptide therapeutic landscape, including historical perspectives, molecular characteristics, regulatory benchmarks, and a therapeutic area breakdown. © 2017.
Maybauer M.O.,University of Texas Medical Branch |
Maybauer M.O.,University of Marburg |
Maybauer D.M.,University of Texas Medical Branch |
Maybauer D.M.,University of Marburg |
And 13 more authors.
Critical Care Medicine | Year: 2014
OBJECTIVE:: To determine if the selective vasopressin type 1a receptor agonist selepressin (FE 202158) is as effective as the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist vasopressor hormone arginine vasopressin when used as a titrated first-line vasopressor therapy in an ovine model of Pseudomonas aeruginosa pneumonia-induced severe sepsis. DESIGN:: Prospective, randomized, controlled laboratory experiment. SETTING:: University animal research facility. SUBJECTS:: Forty-five chronically instrumented sheep. INTERVENTIONS:: Sheep were anesthetized, insufflated with cooled cotton smoke via tracheostomy, and P. aeruginosa were instilled into their airways. They were then placed on assisted ventilation, awakened, and resuscitated with lactated Ringer's solution titrated to maintain hematocrit ± 3% from baseline levels. If, despite fluid management, mean arterial pressure fell by more than 10 mm Hg from baseline level, an additional continuous IV infusion of arginine vasopressin or selepressin was titrated to raise and maintain mean arterial pressure within no less than 10 mm Hg from baseline level. Effects of combination treatment of selepressin with the selective vasopressin V2 receptor agonist desmopressin were similarly investigated. MEASUREMENTS AND MAIN RESULTS:: In septic sheep, MAP fell by ~30 mm Hg, systemic vascular resistance index decreased by ~50%, and ~7 L of fluid were retained over 24 hours; this fluid accumulation was partially reduced by arginine vasopressin and almost completely blocked by selepressin; and combined infusion of selepressin and desmopressin increased fluid accumulation to levels similar to arginine vasopressin treatment. CONCLUSIONS:: Resuscitation with the selective vasopressin type 1a receptor agonist selepressin blocked vascular leak more effectively than the mixed vasopressin type 1a receptor/vasopressin V2 receptor agonist arginine vasopressin because of its lack of agonist activity at the vasopressin V2 receptor. © 2014 by the Society of Critical Care Medicine.
News Article | February 15, 2017
SAINT-PREX, Switzerland--(BUSINESS WIRE)--Ferring today announced the recipients of the 2016-2017 Ferring Innovation Grants program, an annual initiative of the Ferring Research Institute (FRI) which provides grants of up to $100,000 for early stage research. The program focuses on novel extracellular drug targets addressable with peptides or proteins within Ferring’s core therapeutic areas: reproductive health, gastroenterology, urology, and endocrinology. The 2016-2017 awardees and their research subjects are: Stuart Brierley - Flinders University, Australia Venom-derived NaV1.1 inhibitors as novel candidates for treating chronic visceral pain associated with IBS James Deane - Hudson Institute of Medical Research, Australia Investigating the requirement for Notch and Hedgehog signalling in the endometrial stem/progenitor populations that cause endometriosis Marie van Dijk - University of Amsterdam, Netherlands ELABELA as a potential biomarker and therapeutic for pre-eclampsia Florenta Kullmann - University of Pittsburgh, USA Artemin: a novel target for treatment of interstitial cystitis/bladder pain syndrome Mireille Lahoud - Monash University, Australia The development of Clec12A-ligands as a therapeutic approach to regulate gastrointestinal inflammation Padma Murthi - Monash University, Australia Investigating the role of novel peptide receptor as an effective target to improve placental function in preeclampsia Markus Muttenthaler - The University of Queensland, Australia Mapping the location and function of oxytocin and vasopressin receptors throughout the gut Rodrigo Pacheco – Fundación Ciencia & Vida and Universidad Andres Bello, Santiago, Chile Targeting heteromers formed by G-protein coupled receptors involved in the gut-homing of T-cells in inflammatory bowel diseases Aritro Sen – The University of Rochester, USA Regulation of AMH expression by GDF9+BMP15 and FSH during follicular development as a novel therapeutic option “We look forward to the outcomes of the research being carried out by our grant awardees,” said Keith James, President of FRI and Senior Vice President, Research and Development. “Ferring is committed to stimulating basic research, with the ultimate aim of developing innovative products that improve the lives of patients.” Applications for the 2017-2018 Ferring Innovation Grants programme will open in spring/summer 2017. For more information on this year’s program, visit www.ferring-research.com/ferring-grants. About Ferring Research Institute Inc Located in San Diego, California Ferring Research Institute Inc. (FRI) is the global peptide therapeutics research center for Ferring Pharmaceuticals. FRI is committed to building a portfolio of novel, innovative peptide-based drugs and biologicals to address the high unmet medical need for patients in our therapeutic areas of interest. For more detailed information please visit www.ferring-research.com. About Ferring Pharmaceuticals Headquartered in Switzerland, Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group active in global markets. The company identifies, develops and markets innovative products in the areas of reproductive health, urology, gastroenterology, endocrinology and orthopaedics. Ferring has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries. To learn more about Ferring or its products please visit www.ferring.com.
He X.,Free University of Colombia |
He X.,Sun Yat Sen University |
Su F.,Free University of Colombia |
Taccone F.S.,Free University of Colombia |
And 7 more authors.
Critical Care Medicine | Year: 2016
Objective: Selective vasopressin V1A receptor agonists may have advantages over arginine vasopressin in the treatment of septic shock. We compared the effects of selepressin, a selective V1A receptor agonist, arginine vasopressin, and norepinephrine on hemodynamics, organ function, and survival in an ovine septic shock model. Design: Randomized animal study. Setting: University hospital animal research laboratory. Subjects: Forty-six adult female sheep. Interventions: Fecal peritonitis was induced in the anesthetized, mechanically ventilated, fluid-resuscitated sheep, and they were randomized in two successive phases. Three late-intervention groups (each n = 6) received IV selepressin (1 pmol/kg/min), arginine vasopressin (0.25 pmol [0.1 mU]/kg/min), or norepinephrine (3 nmol [0.5 μg]/kg/min) when mean arterial pressure remained less than 70 mm Hg despite fluid challenge; study drugs were thereafter titrated to keep mean arterial pressure at 70-80 mm Hg. Three early-intervention groups (each n = 7) received selepressin, arginine vasopressin, or norepinephrine at the same initial infusion rates as for the late intervention, but already when mean arterial pressure had decreased by 10% from baseline; doses were then titrated as for the late intervention. A control group (n = 7) received saline. All animals were observed until death or for a maximum of 30 hours. Measurements and Main Results: In addition to hemodynamic and organ function assessment, plasma interleukin-6 and nitrite/nitrate levels were measured. In the late-intervention groups, selepressin delayed the decrease in mean arterial pressure and was associated with lower lung wet/dry weight ratios than in the other two groups. In the early-intervention groups, selepressin maintained mean arterial pressure and cardiac index better than arginine vasopressin or norepinephrine, slowed the increase in blood lactate levels, and was associated with less lung edema, lower cumulative fluid balance, and lower interleukin-6 and nitrite/nitrate levels. Selepressin-treated animals survived longer than the other animals. Conclusions: In this clinically relevant model, selepressin, a selective V1A receptor agonist, was superior to arginine vasopressin and to norepinephrine in the treatment of septic shock, especially when administered early. Copyright © 2015 by the Society of Criti.
Fernandez-Varo G.,University of Barcelona |
Oro D.,University of Barcelona |
Cable E.E.,Ferring Research Institute Inc. |
Reichenbach V.,University of Barcelona |
And 6 more authors.
Hepatology | Year: 2016
Patients and rats with cirrhosis and ascites have portal hypertension and circulatory dysfunction. Synthetic arginine vasopressin (AVP) receptor agonists able to induce systemic and mesenteric vasoconstriction have shown their usefulness in reducing portal pressure (PP) in this condition. We assessed the potential therapeutic value of a new V1 a-AVP receptor partial agonist with a preferential splanchnic vasoconstrictor effect (FE 204038) in rats with cirrhosis and ascites. The hemodynamic effects of cumulative intravenous doses of FE 204038, terlipressin, or vehicle were investigated. Mean arterial pressure and PP were continuously recorded and cardiac output and systemic vascular resistance (SVR) assessed at 30-minute intervals for 90 minutes. Urine volume, urine osmolality, and urinary excretion of sodium and creatinine were measured in basal conditions and following twice-daily subcutaneous doses of FE 204038 or vehicle. PP, mean arterial pressure, cardiac output, SVR, and ascites volume were also measured after 6 days. The expression of an array of vasoactive genes was assessed in the thoracic aorta and the mesenteric circulation of control rats and rats with cirrhosis and ascites. FE 204038 dose-dependently decreased PP, did not modify mean arterial pressure, and increased SVR. The effect of the V1a-AVP receptor partial agonist on PP was associated with an improvement in urine volume and urinary excretion of sodium during the first day of treatment. SVR was higher and cardiac output and ascites volume were lower in rats with cirrhosis and ascites treated with FE 204038. V1a-AVP receptor expression in rats with cirrhosis and ascites was markedly enhanced in the mesenteric circulation compared to the thoracic aorta. Conclusion: FE 204038 increases sodium excretion and reduces portal hypertension and ascites in experimental cirrhosis. V1a-AVP receptor partial agonism could be a useful pharmacological treatment in decompensated patients with cirrhosis. © 2016 by the American Association for the Study of Liver Diseases.
Bhat A.,Ipsen |
Roberts L.R.,Pfizer |
Dwyer J.J.,Ferring Research Institute Inc.
European Journal of Medicinal Chemistry | Year: 2015
Peptide macrocycles represent a chemical space where the best of biological tools can synergize with the best of chemical approaches in the quest for leads against undruggable targets. Peptide macrocycles offer some key advantages in both lead discovery and lead optimization phases of drug discovery when compared to natural product and synthetic macrocycles. In addition, they are uniquely positioned to capitalize on the therapeutic potential of peptides because cyclization can help drive selectivity, potency and overcome the common limitations of metabolic instability of peptides. © 2014 Elsevier Masson SAS.
PubMed | Ferring Research Institute Inc. and University of North Carolina at Chapel Hill
Type: | Journal: Peptides | Year: 2016
Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) are potent vasodilator peptides and serve as ligands for the G-protein coupled receptor (GPCR) calcitonin receptor-like receptor (CLR/Calcrl). Three GPCR accessory proteins called receptor activity-modifying proteins (RAMPs) modify the ligand binding affinity of the receptor such that the CLR/RAMP1 heterodimer preferably binds CGRP, while CLR/RAMP2 and CLR/RAMP3 have a stronger affinity for AM. Here we determine the contribution of each of the three RAMPs to blood pressure control in response to exogenous AM and CGRP by measuring the blood pressure of mice with genetic reduction or deletion of the receptor components. Thus, the cardiovascular response of Ramp1