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Genomes and Genes | Denis RiendeauSummaryAffiliation: Merck Research Laboratories Country: USA Publications
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Publications
Etoricoxib (MK-0663): preclinical profile and comparison with other agents that selectively inhibit cyclooxygenase-2D Riendeau
Department of Pharmacology, Biochemistry, and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada
J Pharmacol Exp Ther 296:558-66. 2001....- Microsomal prostaglandin E synthase-1 is a major terminal synthase that is selectively up-regulated during cyclooxygenase-2-dependent prostaglandin E2 production in the rat adjuvant-induced arthritis modelDavid Claveau
Department of Biochemistry, Merck Frosst Center for Therapeutic Research, Kirkland, Quebec, Canada
J Immunol 170:4738-44. 2003..These results show that mPGES-1 is up-regulated throughout the development of AIA and suggest that it plays a major role in the elevated production of PGE(2) in this model... - Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886Denis Riendeau
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada H9H 3L1
Bioorg Med Chem Lett 15:3352-5. 2005..They also block the production of PGE2 in cell based assays but with a decreased potency and more limited selectivity compared to the enzyme assays... - Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2Denis Riendeau
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, Quebec, Canada H9H 3L1
Bioorg Med Chem Lett 14:1201-3. 2004..The (2S,1'R,2'S)-trans-alcohol derivative was found to be the most active metabolite and to be a potent and nonselective inhibitor of COX-2 and COX-1 in both enzyme and human whole blood assays... 
Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitorsAndre Giroux
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada H9H 3L1
Bioorg Med Chem Lett 19:5837-41. 2009..Both active and selective mPGES-1 inhibitors (26 and 44) have a relatively distinct pharmacokinetic profile and are suitable for clinical development...- MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a selective microsomal prostaglandin E synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammationDaigen Xu
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, QC, Canada H9H 3L1
J Pharmacol Exp Ther 326:754-63. 2008..Our data demonstrate that mPGES-1 inhibition leads to effective relief of both pyresis and inflammatory pain in preclinical models of inflammation and may be a useful approach for treating inflammatory diseases... - The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin KJacques Yves Gauthier
Merck Frosst Centre for Therapeutic Research, 16711 Transcanada Hwy, Kirkland, Que, Canada
Bioorg Med Chem Lett 18:923-8. 2008..Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors... - The discovery of MK-0674, an orally bioavailable cathepsin K inhibitorElise Isabel
Merck Frosst Centre for Therapeutic Research, 16711 Transcanada Hwy, Kirkland, Quebec, Canada H9H 3L1
Bioorg Med Chem Lett 20:887-92. 2010..From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards... - Substituted 2,2-bisaryl-bicycloheptanes as novel and potent inhibitors of 5-lipoxygenase activating proteinDwight MacDonald
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada H9H 3L1
Bioorg Med Chem Lett 18:2023-7. 2008..V. dose of 2.5 microg/kg/min). This compound inhibits calcium ionophore stimulated LTB(4) production in both human polymorphonuclear (PMN) leukocytes and human whole blood (IC(50)=2.0 and 33 nM, respectively)... - 3,4-Diaryl-5-hydroxyfuranones: highly selective inhibitors of cyclooxygenase-2 with aqueous solubilityW Cameron Black
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire Dorval, Quebec, Canada H9R 4P8
Bioorg Med Chem Lett 13:1195-8. 2003..These molecules can be converted into their sodium salts which are water soluble, facilitating intravenous formulation. These salts show excellent potency in rat models of pain, fever and inflammation... - Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivityJean-Pierre Falgueyret
Department of Biochemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada
J Med Chem 48:7535-43. 2005..Therefore, basic cathepsin K inhibitors, such as 1, suffer from reduced functional selectivities compared to those predicted using purified enzyme assays... - Deletion of microsomal prostaglandin E2 (PGE2) synthase-1 reduces inducible and basal PGE2 production and alters the gastric prostanoid profileLouise Boulet
Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec H9H 3L1, Canada
J Biol Chem 279:23229-37. 2004.... - Photo-crosslinking of proteins in intact cells reveals a dimeric structure of cyclooxygenase-2 and an inhibitor-sensitive oligomeric structure of microsomal prostaglandin E2 synthase-1Pierre Olivier Hétu
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Que, Canada
Arch Biochem Biophys 477:155-62. 2008..Our data indicate that COX-2 forms a dimer in intact cells and that mPGES-1 has an oligomeric structure that can be disrupted by a selective inhibitor... - Substituted phenanthrene imidazoles as potent, selective, and orally active mPGES-1 inhibitorsBernard Cote
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada
Bioorg Med Chem Lett 17:6816-20. 2007..42 microM (50% FBS) and a human whole blood IC(50) of 1.3 microM. It exhibited a significant analgesic effect in a guinea pig hyperalgesia model when orally dosed at 30 and 100mg/kg... - Carrageenan-induced paw edema in rat elicits a predominant prostaglandin E2 (PGE2) response in the central nervous system associated with the induction of microsomal PGE2 synthase-1Jocelyne Guay
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec H9H 3L1, Canada
J Biol Chem 279:24866-72. 2004..The data also indicate that the up-regulation of mPGES-1 contributes to COX-2-mediated PGE(2) production in the CNS during peripheral inflammation... - Trisubstituted ureas as potent and selective mPGES-1 inhibitorsJean Francois Chiasson
Merck Frosst Center for Therapeutic Research, Kirkland, Quebec, Canada
Bioorg Med Chem Lett 21:1488-92. 2011..34 μM) and in human whole blood assay (IC(50) of 2.1 μM). An efficient and versatile one-pot strategy for the formation of ureas, involving a reductive amination, was developed to generate these inhibitors... - Biarylimidazoles as inhibitors of microsomal prostaglandin E2 synthase-1Tom Y H Wu
Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada
Bioorg Med Chem Lett 20:6978-82. 2010..A series of inhibitors bearing a biaryl imidazole scaffold exhibits excellent inhibition of PGE(2) production in enzymatic and cell-based assays. The synthesis of these molecules and their activities will be discussed... - In vivo inhibition of serine protease processing requires a high fractional inhibition of cathepsin CNathalie Methot
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Quebec, Canada
Mol Pharmacol 73:1857-65. 2008.... - Substituted coumarins as potent 5-lipoxygenase inhibitorsErich L Grimm
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Que, Canada H9H 3L1
Bioorg Med Chem Lett 16:2528-31. 2006..A novel series of substituted coumarin derivatives has been synthesized and the structure-activity relationship was evaluated with respect to their ability to inhibit the formation of leukotrienes via the human 5-lipoxygenase enzyme... - Expression, purification and characterization of recombinant human microsomal PGE2 synthase-1Marc Ouellet
Department of Biochemistry and Molecular Biology, Merck Frosst Canada, Kirkland, Quebec
Adv Exp Med Biol 525:113-6. 2003 - Prostacyclin antagonism reduces pain and inflammation in rodent models of hyperalgesia and chronic arthritisAnne-Marie Pulichino
Merck Frosst Centre for Therapeutic Research, Kirkland, , Canada
J Pharmacol Exp Ther 319:1043-50. 2006..The results also suggest that the inhibition of PGI(2) synthesis by NSAIDs and COX-2 inhibitors, in addition to that of PGE(2), contributes to their efficacy in treating the signs of arthritis... - Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processingNathalie Methot
Department of Biochemistry and Molecular Biology, Merck Research Laboratories, 16711 Trans Canada Highway, Kirkland Quebec H9H 3L1, Canada
J Biol Chem 282:20836-46. 2007.... - Effect of cathepsin k inhibitor basicity on in vivo off-target activitiesSylvie Desmarais
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, P O Box 1005, Pointe Claire Dorval, Quebec, Canada
Mol Pharmacol 73:147-56. 2008..In conclusion, basic cathepsin K inhibitors demonstrate increased off-target cysteine cathepsin activities than their nonbasic analogs and potentially have a greater risk of adverse effects associated with inhibition of these cathepsins... - Identification of a potent and selective non-basic cathepsin K inhibitorChun Sing Li
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire Dorval, Que, Canada H9R 4P8
Bioorg Med Chem Lett 16:1985-9. 2006..The volumes of distribution close to unity were consistent with this compound not being lysosomotropic, which is a characteristic of basic cathepsin K inhibitors... - Discovery of a potent and selective COX-2 inhibitor in the alkoxy lactone series with optimized metabolic profileYves Leblanc
Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire Dorval, Quebec, Canada
Bioorg Med Chem Lett 12:3317-20. 2002.... - Pyridazinones as selective cyclooxygenase-2 inhibitorsChun Sing Li
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire Dorval, Quebec, Canada H9R 4P8
Bioorg Med Chem Lett 13:597-600. 2003..Pyridazinone was found to be an excellent core template for selective COX-2 inhibitors. Two potent, selective and orally active COX-2 inhibitors, which were highly efficacious in rat paw edema and rat pyresis models, have been obtained... - An activity-based probe for the determination of cysteine cathepsin protease activities in whole cellsJean-Pierre Falgueyret
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Que, Canada
Anal Biochem 335:218-27. 2004..These whole-cell enzyme occupancy assays are useful to determine the cellular permeability of competing inhibitors and have the advantage of not requiring specific substrates for each cathepsin of interest... 
Cyclo-oxygenase-2 contributes to constitutive prostanoid production in rat kidney and brainPierre Olivier Hétu
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway, Kirkland, QC, Canada H9H 3L1
Biochem J 391:561-6. 2005....- Down-regulation of microsomal prostaglandin E2 synthase-1 in adipose tissue by high-fat feedingPierre Olivier Hétu
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Hwy, Kirkland, Quebec, Canada H9H 3L1
Obesity (Silver Spring) 15:60-8. 2007..This work was, thus, undertaken to study the regulation of the various PGE2 synthases (PGESs) in obesity... - Purification and characterization of recombinant microsomal prostaglandin E synthase-1Marc Ouellet
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, P O Box 1005, Pointe Claire Dorval, Kirkland, Que, Canada H9R 4P8
Protein Expr Purif 26:489-95. 2002..The results show that purified mPGES-1 has a specific activity similar to Cox-2, consistent with its postulated role in Cox-2 mediated PGE(2) formation... - Inhibition of inducible prostaglandin E(2) synthase by 15-deoxy-Delta(12,14)-prostaglandin J(2) and polyunsaturated fatty acidsOmar Quraishi
Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Kirkland, Que, Canada
Biochem Pharmacol 63:1183-9. 2002.... - Characterization of a stable, hypertensive rat model suitable for the consecutive evaluation of human renin inhibitorsRene St-Jacques
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Canada
J Renin Angiotensin Aldosterone Syst 12:133-45. 2011..Here, we characterise a variation of this model in which animals present stable hypertension... - Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin KJames T Palmer
Celera Genomics, Inc, 180 Kimball Way, South San Francisco, California 94080, USA
J Med Chem 48:7520-34. 2005..Inhibition of collagen breakdown by cathepsin K inhibitors suggests this mechanism of action may be useful in osteoporosis and other indications involving bone resorption... - Action of cyclooxygenase inhibitors and a leukotriene biosynthesis inhibitor on cisplatin-induced acute and delayed emesis in the ferretTasia S W Sam
Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China
J Pharmacol Sci 103:189-200. 2007..p., three times per day; P<0.05). Inhibition of the cyclooxygenase and lipoxygenase pathways does not account for the anti-emetic of dexamethasone... - Double-label expression studies of prostacyclin synthase, thromboxane synthase and COX isoforms in normal aortic endotheliumDouglas W Kawka
Departments of Immunology and Rheumatology, Merck Research Laboratories, Rahway, NJ 07065, USA
Biochim Biophys Acta 1771:45-54. 2007..The extensive co-localization of PGIS and COX-2 in the lung also indicates significant tissue differences in the co-expression patterns of these two enzymes... - Cyclooxygenase-2 promotes early atherosclerotic lesion formation in LDL receptor-deficient miceMichael E Burleigh
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tenn, USA
Circulation 105:1816-23. 2002....