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Schering-Plough Corporation was a United States-based pharmaceutical company. It was founded in 1851 by Ernst Christian Friedrich Schering as Schering AG in Germany. In 1971, the Schering Corporation merged with Plough to form Schering-Plough. On November 4, 2009 Merck & Co. merged with Schering-Plough with the new company taking the name of Merck & Co.Schering-Plough manufactured several pharmaceutical drugs, the most well-known of which were the allergy drugs Claritin and Clarinex, an anti-cholesterol drug Vytorin, and a brain tumor drug Temodar. These are now available from Merck & Co.Schering Plough also owned and operated the major foot care brand name Dr. Scholl's and the skin care line Coppertone. These also became a part of the new company.As of June 2005, Schering-Plough had 1.4% market share in the U.S., placing it seventeenth in the top twenty pharmaceutical corporations by sales compiled by IMS Health.Schering-Plough was a full member of the European Federation of Pharmaceutical Industries and Associations , a membership which is also maintained by the new Merck. Wikipedia.


Mentink A.,University of Twente | Hulsman M.,Technical University of Delft | Groen N.,University of Twente | Licht R.,University of Twente | And 8 more authors.
Biomaterials | Year: 2013

Mesenchymal stromal cells (hMSCs) are advancing into the clinic but the therapeutic efficacy of hMSCs faces the problem of donor variability. In bone tissue engineering, no reliable markers have been identified which are able to predict the bone-forming capacity of hMSCs prior to implantation. To this end, we isolated hMSCs from 62 donors and characterized systematically their in vitro lineage differentiation capacity, gene expression signature and in vivo capacity for ectopic bone formation. Our data confirms the large variability of in vitro differentiation capacity which did not correlate with in vivo ectopic bone formation. Using DNA microarray analysis of early passage hMSCs we identified a diagnostic bone-forming classifier. In fact, a single gene, CADM1, strongly correlated with the bone-forming capacity of hMSCs and could be used as a reliable in vitro diagnostic marker. Furthermore, data mining of genes expressed correlating with in vivo bone formation represented involvement in neurogenic processes and Wnt signaling. We will apply our data set to predict therapeutic efficacy of hMSCs and to gain novel insight in the process of bone regeneration. Our bio-informatics driven approach may be used in other fields of cell therapy to establish diagnostic markers for clinical efficacy. © 2013 Elsevier Ltd. Source


Vottero E.,VU University Amsterdam | Rea V.,VU University Amsterdam | Lastdrager J.,VU University Amsterdam | Honing M.,Schering Plough Research Institute | And 2 more authors.
Journal of Biological Inorganic Chemistry | Year: 2011

CYP102A1, originating from Bacillus megaterium, is a highly active enzyme which has attracted much attention because of its potential applicability as a biocatalyst for oxidative reactions. Previously we developed drug-metabolizing mutant CYP102A1 M11 by a combination of site-directed and random mutagenesis. CYP102A1 M11 contains eight mutations, when compared with wild-type CYP102A1, and is able to produce human-relevant metabolites of several pharmaceuticals. In this study, active-site residue 87 of drug-metabolizing mutant CYP102A1 M11 was mutated to all possible natural amino acids to investigate its role in substrate selectivity and regioselectivity. With alkoxyresorufins as substrates, large differences in substrate selectivities and coupling efficiencies were found, dependent on the nature of residue 87. For all combinations of alkoxyresorufins and mutants, extremely fast rates of NADPH oxidation were observed (up to 6,000 min -1). However, the coupling efficiencies were extremely low: even for the substrates showing the highest rates of O-dealkylation, coupling efficiencies were lower than 1%. With testosterone as the substrate, all mutants were able to produce three hydroxytestosterone metabolites, although with different activities and with remarkably different product ratios. The results show that the nature of the amino acid at position 87 has a strong effect on activity and regioselectivity in the drug-metabolizing mutant CYP102A1 M11. Because of the wide substrate selectivity of CYP102A1 M11 when compared with wild-type CYP102A1, this panel of mutants will be useful both as biocatalysts for metabolite production and as model proteins for mechanistic studies on the function of P450s in general. © 2011 The Author(s). Source


Bovee T.F.H.,RIKILT Institute of Food Safety | Thevis M.,German Sport University Cologne | Hamers A.R.M.,RIKILT Institute of Food Safety | Peijnenburg A.A.C.M.,RIKILT Institute of Food Safety | And 3 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2010

Selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs) are compounds that activate their cognate receptor in particular target tissues without affecting other organs. Many of these compounds will find their use in therapeutic treatments. However, they also will have a high potential for misuse in veterinary practice and the sporting world. Here we demonstrate that yeast estrogen and androgen bioassays can be used to detect SERMs and SARMs, and are also useful screening tools to investigate their mode of action. Six steroidal 11β-substituents of E2 (SERMs) and some arylpropionamide- and quinoline-based SARMs were tested. In addition, 7 compounds previously tested on AR agonism and determined as inactive in the yeast androgen bioassay, while QSAR modelling revealed strong binding to the human androgen receptor, are now shown to act as AR antagonists. © 2009 Elsevier Ltd. All rights reserved. Source


Bonger K.M.,Leiden University | Kapoerchan V.V.,Leiden University | Grotenbreg G.M.,Leiden University | Van Koppen C.J.,Schering Plough Research Institute | And 3 more authors.
Organic and Biomolecular Chemistry | Year: 2010

Oligoprolines (OPs) are used as rigid backbone scaffolds for the design of oligomeric ligands that target specific G protein-coupled receptors. The OPs were designed to vary in length, the position and number of the ligand-functionalized residues incorporated. For all synthesized compounds a typical PP type II helix was evidenced by circular dichroism indicating that decoration of the helix with large ligands did not affect the helical conformation. Pharmacological evaluation revealed that oligomerization of an agonist with the use of an oligoproline scaffold showed an increase in potency when compared to the monomeric counterparts. © 2010 The Royal Society of Chemistry. Source


Verkaar F.,Schering Plough Research Institute | Verkaar F.,Maastricht University | Blankesteijn W.M.,Maastricht University | Smits J.F.M.,Maastricht University | Zaman G.J.R.,Schering Plough Research Institute
FASEB Journal | Year: 2010

Wnt/β-catenin signaling is an important regulator of cell polarity, proliferation, and stem cell maintenance during development and adulthood. Wnt proteins induce the nuclear accumulation of β-catenin, which regulates the expression of Wnt-responsive genes through association with TCF/LEF transcription factors. Aberrant Wnt/β-catenin signaling has been implicated in a plethora of pathologies and, most notably, underlies initiation and expansion of several cancers. Here, we apply enzyme fragment complementation to measure the nuclear accumulation of β-catenin. β-Catenin was tagged with a peptide fragment of β-galactosidase and transfected into cells expressing a corresponding deletion mutant of the enzyme exclusively in the nucleus. Stimulation of the cells with recombinant Wnt-3a restored β-galactosidase activity in a dose-dependent manner with nanomolar potency. Using the assay, we confirmed that Wnt-5a represses β-catenin-driven reporter gene activity downstream of nuclear entry of β-catenin. In addition, we tested a library of >2000 synthetic chemical compounds for their ability to induce β-catenin nuclear accumulation. The immunosuppressive protein kinase C inhibitor sotrastaurin (AEB-071) was identified as an activator of Wnt/β-catenin signaling at micromolar concentrations. It was confirmed that the compound stabilizes endogenous β-catenin protein and can induce TCF/LEF-dependent gene transcription. Subsequent biochemical profiling of >200 kinases revealed both isoforms of glycogen synthase kinase 3, as previously unappreciated targets of sotrastaurin. We show that the β-catenin nuclear accumulation assay contributes to our knowledge of molecular interactions within the Wnt/β-catenin pathway and can be used to find new therapeutics targeting Wnt/β-catenin signaling. © FASEB. Source

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