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Genomes and GenesSpecies | Oliver WerzSummaryAffiliation: Frankfurt am Main Country: Germany Publications
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Publications
5-Lipoxygenase activation by MAPKAPK-2 and ERKsOliver Werz
Institute of Pharmaceutical Chemistry, University of Frankfurt, Germany
Adv Exp Med Biol 525:129-32. 2003- Extracellular signal-regulated kinases phosphorylate 5-lipoxygenase and stimulate 5-lipoxygenase product formation in leukocytesOliver Werz
Institute of Pharmaceutical Chemistry, University of Frankfurt, D 60439 Frankfurt, Germany
FASEB J 16:1441-3. 2002..Finally, the data suggest that ERKs and p38 MAPK-regulated MAPKAPKs can act in conjunction to stimulate 5-LO by phosphorylation... - Activation of 5-lipoxygenase by cell stress is calcium independent in human polymorphonuclear leukocytesOliver Werz
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
Blood 99:1044-52. 2002..This mechanism could function independently of Ca(++)-mediated 5-LO activation for stimulation of leukotriene biosynthesis under physiologic conditions as well as in inflammatory diseases... - Suppression of receptor-mediated Ca2+ mobilization and functional leukocyte responses by hyperforinChristian Feisst
Institute of Pharmaceutical Chemistry, University of Frankfurt, D 60439 Frankfurt, Germany
Biochem Pharmacol 67:1531-9. 2004..Our data suggest that hyperforin targets component(s) within G protein signaling cascades that regulate Ca(2+) homeostasis, coupled to proinflammatory leukocyte functions... - 5-lipoxygenase: cellular biology and molecular pharmacologyOliver Werz
Institute of Pharmaceutical Chemistry, University of Frankfurt, D 60439 Frankfurt, Germany
Curr Drug Targets Inflamm Allergy 1:23-44. 2002..This review highlights the determinants of cellular 5-LO activity and summarizes the molecular pharmacology of 5-LO... 
Hyperforin is a novel type of 5-lipoxygenase inhibitor with high efficacy in vivoChristian Feisst
Institute of Pharmaceutical Chemistry, University of Frankfurt, Max von Laue Str 9, 60438 Frankfurt, Germany
Cell Mol Life Sci 66:2759-71. 2009..Together, hyperforin is a novel type of 5-LO inhibitor apparently acting by interference with the C2-like domain, with high effectiveness in vivo...- Phosphorylation- and stimulus-dependent inhibition of cellular 5-lipoxygenase activity by nonredox-type inhibitorsLutz Fischer
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany
FASEB J 17:949-51. 2003.... - SAR studies of acidic dual γ-secretase/PPARγ modulatorsMartina Hieke
Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max von Laue Str 9, D 60438 Frankfurt am Main, Germany
Bioorg Med Chem 19:5372-82. 2011..Compound 17 showed an IC(50) Aβ42=2.4 μM and an EC(50) PPARγ=7.2 μM and could be a valuable tool to further evaluate the concept of dual γ-secretase/PPARγ modulators in animal models of Alzheimer's disease... 
Coupling of boswellic acid-induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytesAnja Altmann
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, Frankfurt D-60439, Germany
Br J Pharmacol 141:223-32. 2004....- Induction of central signalling pathways and select functional effects in human platelets by beta-boswellic acidDaniel Poeckel
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, Frankfurt D-60439, Germany
Br J Pharmacol 146:514-24. 2005..In summary, beta-BA potently induces Ca2+ mobilisation as well as the activation of pivotal protein kinases, and elicits functional platelet responses such as thrombin generation, liberation of AA, and aggregation... - Discovery and biological evaluation of a novel class of dual microsomal prostaglandin E2 synthase-1/5-lipoxygenase inhibitors based on 2-[(4,6-diphenethoxypyrimidin-2-yl)thio]hexanoic acidMartina Hieke
Institute of Pharmaceutical Chemistry, ZAFES LiFF Goethe University Frankfurt, Frankfurt am Main, Germany
J Med Chem 54:4490-507. 2011..Together, we provide novel promising lead compounds for the treatment of inflammatory diseases valuable for further investigations in vivo... - Inhibitors of actin polymerisation stimulate arachidonic acid release and 5-lipoxygenase activation by upregulation of Ca2+ mobilisation in polymorphonuclear leukocytes involving Src family kinasesLutz Fischer
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany
Biochim Biophys Acta 1736:109-19. 2005..We conclude that in PMNL, inhibitors of actin polymerisation cause enhancement of intracellular Ca2+ levels through Src family kinase signaling, thereby facilitating stimulus-induced release of AA and 5-LO product formation... - Monocyte-derived soluble protein confers 5-lipoxygenase activity Ca2+-dependentEva Bürkert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
Biochem Biophys Res Commun 295:985-91. 2002..Further characterization showed that this factor is a 80-100 kDa heat-sensitive protein... - Cell type-dependent activation of 5-lipoxygenase by arachidonic acidEva Bürkert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
J Leukoc Biol 73:191-200. 2003..Instead, 5-LO activation in MM6 cells required Ca2+ or alternative signaling pathways induced by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ considerably between cell types... - The C2-like beta-barrel domain mediates the Ca2+-dependent resistance of 5-lipoxygenase activity against inhibition by glutathione peroxidase-1Eva Bürkert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
J Biol Chem 278:42846-53. 2003..In summary, our data suggest that interaction of Ca2+ at the C2-like domain of 5-LO protects the enzyme against the effect of GPx-1. Apparently, in the presence of Ca2+, a low lipid hydroperoxide level is sufficient for 5-LO activation... - 1-Oleoyl-2-acetylglycerol stimulates 5-lipoxygenase activity via a putative (phospho)lipid binding site within the N-terminal C2-like domainChristina Hörnig
Institute of Pharmaceutical Chemistry, ZAFES, University of Frankfurt, D 60439 Frankfurt, Germany
J Biol Chem 280:26913-21. 2005..We conclude that OAG directly stimulates 5-LO by acting at a phospholipid binding site located within the C2-like domain... - Induction of 5-lipoxygenase activation in polymorphonuclear leukocytes by 1-oleoyl-2-acetylglycerolDana Albert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str 9, D-60439, Frankfurt, Germany
Biochim Biophys Acta 1631:85-93. 2003..Together, OAG acts as a direct agonist for 5-LO product synthesis in PMNL stimulating 5-LO by novel undefined mechanisms... - The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytesDana Albert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
J Leukoc Biol 83:1019-27. 2008..Together, our data suggest that in agonist-stimulated PMNL, the endogenous formation of DAGs via the PLD/PA-P pathway determines 5-LO activation... - Analysis of the 5-lipoxygenase promoter and characterization of a vitamin D receptor binding siteBernd L Sorg
Institute of Pharmaceutical Chemistry ZAFES, University of Frankfurt, Marie Curie Str 9, D 60439 Frankfurt, Germany
Biochim Biophys Acta 1761:686-97. 2006.... - DNA methylation regulates 5-lipoxygenase promoter activityJohannes Uhl
Institute of Pharmaceutical Chemistry, University of Frankfurt, Germany
Adv Exp Med Biol 525:169-72. 2003 - The aminosteroid phospholipase C antagonist U-73122 (1-[6-[[17-beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione) potently inhibits human 5-lipoxygenase in vivo and in vitroChristian Feisst
Institute of Pharmaceutical Chemistry, University of Frankfurt, Germany
Mol Pharmacol 67:1751-7. 2005..Since 5-LO products induce increases in [Ca2+]i via GPCRs, caution should be used when interpreting data where U-73122 is used as tool to determine a direct role of PLC in receptor-mediated Ca2+ mobilization... - Evaluation of hyperforin analogues for inhibition of 5-lipoxygenaseChristian Feisst
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany
Med Chem 1:287-91. 2005..Our data show that some of the oxidised hyperforin derivatives possess even improved efficacy, whereas alkylation and acylation have detrimental effects... - Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cellsOliver Werz
Institutes of Pharmaceutical Chemistry and Organic Chemistry, University of Frankfurt, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
Proc Natl Acad Sci U S A 102:13164-9. 2005..We suggest that splitting of BL41-E95-A cells induces de novo synthesis of a protein involved in the activation of casp-6, which cleaves 5-LO... - Molecular pharmacological profile of the nonredox-type 5-lipoxygenase inhibitor CJ-13,610Lutz Fischer
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, Frankfurt D-60439, Germany
Br J Pharmacol 142:861-8. 2004..In summary, CJ-13,610 may possess considerable potential as a potent orally active nonredox-type 5-LO inhibitor that lacks certain disadvantages of former representatives of this class of 5-LO inhibitors... - Inhibition of 5-lipoxygenase by U73122 is due to covalent binding to cysteine 416Michael Hörnig
Institute of Pharmaceutical Chemistry ZAFES, University of Frankfurt, Max von Laue Str 9, D 60438 Frankfurt, Germany
Biochim Biophys Acta 1821:279-86. 2012..Together, our data suggest that the area around Cys416 which is close to the proposed AA entry channel to the active site is an interesting target for the development of new 5-LO inhibitors... - Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilizationAnja Altmann
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie Strasse 9, D-60439 Frankfurt, Germany
Biochem Biophys Res Commun 290:185-90. 2002..Our results suggest that 11-keto-BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Ca(2+)... - Hyperforin is a dual inhibitor of cyclooxygenase-1 and 5-lipoxygenaseDana Albert
Institute of Pharmaceutical Chemistry, University of Frankfurt, D-60439 Frankfurt, Germany
Biochem Pharmacol 64:1767-75. 2002.... - Hypertonicity suppresses ionophore-induced product formation and translocation of 5-lipoxygenase in human leukocytesEva Bürkert
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie Curie Strasse 9, D 60439 Frankfurt, Germany
J Leukoc Biol 71:477-86. 2002..In summary, we show that hypertonicity blocks agonist-induced release of AA, 5-LO product formation, and translocation and in parallel, prevents activation of p38 MAPK and downstream 5-LO kinases in leukocytes... - Identification of molecular targets of the oligomeric nonprenylated acylphloroglucinols from Myrtus communis and their implication as anti-inflammatory compoundsChristian Feisst
Institute of Pharmaceutical Chemistry, University of Frankfurt, Frankfurt, Germany
J Pharmacol Exp Ther 315:389-96. 2005.... - Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincenseLars Tausch
Institute of Pharmaceutical Chemistry, Johann Wolfgang Goethe University Frankfurt, Frankfurt, Germany
J Immunol 183:3433-42. 2009..In conclusion, we show that catG is a functional and pharmacologically relevant target of BAs, and interference with catG could explain some of the anti-inflammatory properties of frankincense... - Myrtucommulone from Myrtus communis induces apoptosis in cancer cells via the mitochondrial pathway involving caspase-9Irina Tretiakova
Institute of Pharmaceutical Chemistry, University of Frankfurt, Max von Laue Strasse 9, Frankfurt am Main, Germany
Apoptosis 13:119-31. 2008..Conclusively, MC induces apoptosis in cancer cell lines, with marginal cytotoxicity for non-transformed cells, via the mitochondrial cytochrome c/Apaf-1/caspase-9 pathway... - Celecoxib inhibits 5-lipoxygenaseThorsten J Maier
Pharmazentrum frankfurt ZAFES, Institute of Clinical Pharmacology, Johann Wolfgang Goethe University, Theodor Stern Kai 7, 60590 Frankfurt Main, Germany
Biochem Pharmacol 76:862-72. 2008..2 mg/kg. Together, celecoxib is a direct inhibitor of 5-LO in vitro and in vivo. These findings provide a potential molecular basis for some of the described COX-2-independent pharmacological effects of celecoxib... - Development of a method for expression and purification of the regulatory C2-like domain of human 5-lipoxygenaseAngela A Y Michel
Institute of Pharmaceutical Chemistry, University of Frankfurt, Max von Laue Str 9, D 60438 Frankfurt, Germany
Protein Expr Purif 59:110-6. 2008.... - The 5-lipoxygenase promoter is regulated by DNA methylationJohannes Uhl
Institutes of Pharmaceutical Chemistry and Microbiology, University of Frankfurt, Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany
J Biol Chem 277:4374-9. 2002.... - Design, synthesis, and biological evaluation of a novel class of gamma-secretase modulators with PPARgamma activityMartina Hieke
Institute of Pharmaceutical Chemistry, ZAFES LiFF Goethe University Frankfurt, Max von Laue Strasse 9, D 60438 Frankfurt am Main, Germany
J Med Chem 53:4691-700. 2010..0 microM, EC(50)(PPARgamma) = 11.0 microM) and the replacement of the two phenyl residues of 8 by cyclohexyl yielding compound 22 (IC(50)(Abeta42) = 5.1 microM, EC(50)(PPARgamma) = 6.6 microM)... - Development of 5-lipoxygenase inhibitors--lessons from cellular enzyme regulationOliver Werz
Institute of Pharmaceutical Chemistry/ZAFES, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany
Biochem Pharmacol 70:327-33. 2005..This comment focuses on the impact of these stimulatory and inhibitory pathways on the efficacy of 5-LO inhibitors and suggests additional criteria for the development of this class of compounds... - Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cellsDmitry A Aleksandrov
A.N. Belozersky Institute of Physicochemical Biology, Moscow State University, Russia
FEBS J 273:548-57. 2006..The fact that cellular LT production is regulated by sulfated cholesterol highlights a possible regulatory role of sulfotransferases/sulfatases in 5-LO product synthesis... - Therapeutic options for 5-lipoxygenase inhibitorsOliver Werz
Pharmaceutical Institute, , Auf der Morgenstelle 8, , Germany
Pharmacol Ther 112:701-18. 2006..In this review, we summarize the knowledge on possible functions of the 5-LO pathway in various diseases like asthma, cancer and cardiovascular events and review the corresponding potential therapeutic roles of 5-LO inhibitors... - 3-O-acetyl-11-keto-boswellic acid decreases basal intracellular Ca2+ levels and inhibits agonist-induced Ca2+ mobilization and mitogen-activated protein kinase activation in human monocytic cellsDaniel Poeckel
Department of Pharmaceutical Analysis, Institute of Pharmacy, Eberhard-Karls-University Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
J Pharmacol Exp Ther 316:224-32. 2006..Interruption of these events may represent a possible mechanism underlying the reported anti-inflammatory properties of AKBA... - Inhibition of 5-lipoxygenase product synthesis by natural compounds of plant originOliver Werz
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Tuebingen, Germany
Planta Med 73:1331-57. 2007..In the second part, natural compounds that interfere with 5-LO product formation are compiled and grouped into structural classes, and the underlying molecular mechanisms and structure-activity relationships are discussed... - 5-Lipoxygenase: regulation of expression and enzyme activityOlof Radmark
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S 17177 Stockholm, Sweden
Trends Biochem Sci 32:332-41. 2007..With regard to the control of enzyme activity, many of these findings focus on the N-terminal domain of 5-LO... - Extracellular signal-regulated kinase-2 phosphorylates RORalpha4 in vitroAdriane Lechtken
Institute of Pharmaceutical Chemistry ZAFES, Johann Wolfgang Goethe University Frankfurt, Max von Laue Strasse 9, 60438 Frankfurt am Main, Germany
Biochem Biophys Res Commun 358:890-6. 2007..The RORalpha4-T128A mutant exhibits an increased DNA-binding affinity, an increased transcriptional activity and, in the interplay with the opponent RevErbalpha, acts as a stronger competitor at ROR response elements than RORalpha4-WT... - Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 productionMarija Rakonjac
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S 171 77 Stockholm, Sweden
Proc Natl Acad Sci U S A 103:13150-5. 2006..Furthermore, in stimulated cells, CLP appears to function in a complex together with 5LO and membranes, increasing the capacity of 5LO for leukotriene biosynthesis... - Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2)Oliver Werz
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II, Karolinska Institutet, S 171 77 Stockholm, Sweden
J Biol Chem 277:14793-800. 2002.... - Boswellic acids stimulate arachidonic acid release and 12-lipoxygenase activity in human platelets independent of Ca2+ and differentially interact with platelet-type 12-lipoxygenaseDaniel Poeckel
Department of Pharmaceutical Analytics, Institute of Pharmacy, Eberhard Karls University Tubingen, Auf der Morgenstelle 8, D 72076 Tubingen, Germany
Mol Pharmacol 70:1071-8. 2006.... - Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytesDaniel Poeckel
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tubingen, Auf der Morgenstelle 8, D 72076 Tubingen, Germany
Biochem Pharmacol 76:91-7. 2008..4.21.37). Together, our findings provide a pharmacological basis for the anti-inflammatory properties reported for CS- and CA-containing extracts... - Extraction and visualization of potential pharmacophore points using support vector machines: application to ligand-based virtual screening for COX-2 inhibitorsLutz Franke
, , Marie-Curie-Strasse 9, D-60439 Frankfurt, Germany
J Med Chem 48:6997-7004. 2005..It was demonstrated that the SVM machine-learning method can be used in virtual screening and be analyzed in a human-interpretable way that results in a set of rules for designing novel molecules... - ALOX5 variants associated with susceptibility to human pulmonary tuberculosisFlorian Herb
Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany
Hum Mol Genet 17:1052-60. 2008..003, OR 1.50). Our observation of an association of ALOX5 variants with susceptibility to TB contributes evidence of the importance of 5-LO products to the regulation of immune responses to M. tuberculosis... - Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acidsUlf Siemoneit
Department of Pharmaceutical Analytics, Institute of Pharmacy, Eberhard Karls University Tuebingen, D 72076 Tuebingen, Germany
Biochem Pharmacol 75:503-13. 2008..In conclusion, BAs, in particular AKBA, directly interfere with COX-1 and may mediate their anti-inflammatory actions not only by suppression of lipoxygenases, but also by inhibiting cyclooxygenases, preferentially COX-1... - Identification of natural-product-derived inhibitors of 5-lipoxygenase activity by ligand-based virtual screeningLutz Franke
Institut für Organische Chemie und Chemische Biologie ZAFES, Johann Wolfgang Goethe Universitat, Siesmayerstrasse 70, D 60323 Frankfurt am Main, Germany
J Med Chem 50:2640-6. 2007..The results demonstrate the potential of natural-product-derived screening libraries for hit and lead structure identification... - Inhibition of human 5-lipoxygenase and anti-neoplastic effects by 2-amino-1,4-benzoquinonesDaniel Poeckel
Department of Pharmaceutical Analytics, Institute of Pharmacy, Eberhard-Karls-University Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
Med Chem 2:591-5. 2006..Based on these features, bioactive 2-amino-1,4-benzoquinones may possess potential for the pharmacological treatment of diseases associated with elevated 5-lipoxygenase activity, in particular certain types of cancer... - GC-rich sequences in the 5-lipoxygenase gene promoter are required for expression in Mono Mac 6 cells, characterization of a novel Sp1 binding siteDavid Dishart
Department of Medical Biochemistry and Biophysics, Division of Physiological Chemistry II Karolinska Institutet, S 171 77 Stockholm, Sweden
Biochim Biophys Acta 1738:37-47. 2005..Thus, the GC-rich part of the 5LO gene promoter, including a novel Sp1 site, appear important for basal (rather than upregulated) transcription of 5LO in MM6 cells... - Design and synthesis of novel 2-amino-5-hydroxyindole derivatives that inhibit human 5-lipoxygenaseJens Landwehr
Department of Medicinal Chemistry, Institute for Pharmacy and Food Chemistry at the Emil-Fischer Center, Friedrich Alexander University Erlangen, Schuhstrasse 19, D-91052 Erlangen, Germany
J Med Chem 49:4327-32. 2006..On the basis of their 5-LO inhibitory properties, these novel 2-amino-5-hydroxyindoles represent potential candidates for the pharmacological intervention with LT-associated diseases... - Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acidOliver Werz
Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard Karls University Tuebingen, Auf der Morgenstelle 8, D 72076 Tuebingen, Germany
J Med Chem 51:5449-53. 2008..6 microM). These derivatives may possess potential for intervention with inflammatory and allergic diseases...