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Design of Dual Inhibitors of Soluble Epoxide Hydrolase and LTA4 Hydrolase.

Hiesinger K, Schott A, Kramer JS, Blöcher R, Witt F, Wittmann SK, Steinhilber D, Pogoryelov D, Gerstmeier J, Werz O, Proschak E.

ACS Med Chem Lett. 2019 Oct 30;11(3):298-302. doi: 10.1021/acsmedchemlett.9b00330. eCollection 2020 Mar 12.


Process control and scale-up of modified bacterial cellulose production for tailor-made anti-inflammatory drug delivery systems.

Beekmann U, Schmölz L, Lorkowski S, Werz O, Thamm J, Fischer D, Kralisch D.

Carbohydr Polym. 2020 May 15;236:116062. doi: 10.1016/j.carbpol.2020.116062. Epub 2020 Feb 22.


Differential role of vacuolar (H+)-ATPase in the expression and activity of cyclooxygenase-2 in human monocytes.

Rao Z, Jordan PM, Wang Y, Menche D, Pace S, Gerstmeier J, Werz O.

Biochem Pharmacol. 2020 Feb 14;175:113858. doi: 10.1016/j.bcp.2020.113858. [Epub ahead of print]


Discovery of Novel 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors by Exploiting a Multistep Virtual Screening Protocol.

Olgac A, Carotti A, Kretzer C, Zergiebel S, Seeling A, Garscha U, Werz O, Macchiarulo A, Banoglu E.

J Chem Inf Model. 2020 Mar 23;60(3):1737-1748. doi: 10.1021/acs.jcim.9b00941. Epub 2020 Feb 24.


A Combinatorial Virtual Screening Approach Driving the Synthesis of 2,4-Thiazolidinedione-Based Molecules as New Dual mPGES-1/5-LO Inhibitors.

Lauro G, Terracciano S, Cantone V, Ruggiero D, Fischer K, Pace S, Werz O, Bruno I, Bifulco G.

ChemMedChem. 2020 Mar 18;15(6):481-489. doi: 10.1002/cmdc.201900694. Epub 2020 Feb 17.


Improved Bioactivity of the Natural Product 5-Lipoxygenase Inhibitor Hyperforin by Encapsulation into Polymeric Nanoparticles.

Traeger A, Voelker S, Shkodra-Pula B, Kretzer C, Schubert S, Gottschaldt M, Schubert US, Werz O.

Mol Pharm. 2020 Mar 2;17(3):810-816. doi: 10.1021/acs.molpharmaceut.9b01051. Epub 2020 Feb 7.


Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.

Werner M, Pace S, Czapka A, Jordan PM, Gerstmeier J, Koeberle A, Werz O.

Cell Mol Life Sci. 2020 Jan 1. doi: 10.1007/s00018-019-03413-w. [Epub ahead of print]


Genetic polymorphism rs8193036 of IL17A is associated with increased susceptibility to pulmonary tuberculosis in Chinese Han population.

Wang W, Deng G, Zhang G, Yu Z, Yang F, Chen J, Cai Y, Werz O, Chen X.

Cytokine. 2020 Mar;127:154956. doi: 10.1016/j.cyto.2019.154956. Epub 2019 Dec 18.


Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.

Romp E, Arakandy V, Fischer J, Wolz C, Siegmund A, Löffler B, Tuchscherr L, Werz O, Garscha U.

Cell Mol Life Sci. 2019 Dec 5. doi: 10.1007/s00018-019-03393-x. [Epub ahead of print]


Distinct and overlapping functions of glutathione peroxidases 1 and 2 in limiting NF-κB-driven inflammation through redox-active mechanisms.

Koeberle SC, Gollowitzer A, Laoukili J, Kranenburg O, Werz O, Koeberle A, Kipp AP.

Redox Biol. 2020 Jan;28:101388. doi: 10.1016/j.redox.2019.101388. Epub 2019 Nov 16.


15-Hydroperoxy-PGE2 : Intermediate in Mammalian and Algal Prostaglandin Biosynthesis.

Jagusch H, Werner M, Werz O, Pohnert G.

Angew Chem Int Ed Engl. 2019 Dec 2;58(49):17641-17645. doi: 10.1002/anie.201910461. Epub 2019 Oct 23.


Stereoselective total synthesis of parthenolides indicates target selectivity for tubulin carboxypeptidase activity.

Freund RRA, Gobrecht P, Rao Z, Gerstmeier J, Schlosser R, Görls H, Werz O, Fischer D, Arndt HD.

Chem Sci. 2019 Jun 26;10(31):7358-7364. doi: 10.1039/c9sc01473j. eCollection 2019 Aug 21.


Myxochelin- and Pseudochelin-Derived Lipoxygenase Inhibitors from a Genetically Engineered Myxococcus xanthus Strain.

Sester A, Winand L, Pace S, Hiller W, Werz O, Nett M.

J Nat Prod. 2019 Sep 27;82(9):2544-2549. doi: 10.1021/acs.jnatprod.9b00403. Epub 2019 Aug 29.


Associated Bacteria Affect Sexual Reproduction by Altering Gene Expression and Metabolic Processes in a Biofilm Inhabiting Diatom.

Cirri E, De Decker S, Bilcke G, Werner M, Osuna-Cruz CM, De Veylder L, Vandepoele K, Werz O, Vyverman W, Pohnert G.

Front Microbiol. 2019 Aug 2;10:1790. doi: 10.3389/fmicb.2019.01790. eCollection 2019.


Ginkgolic Acid is a Multi-Target Inhibitor of Key Enzymes in Pro-Inflammatory Lipid Mediator Biosynthesis.

Gerstmeier J, Seegers J, Witt F, Waltenberger B, Temml V, Rollinger JM, Stuppner H, Koeberle A, Schuster D, Werz O.

Front Pharmacol. 2019 Jul 17;10:797. doi: 10.3389/fphar.2019.00797. eCollection 2019.


Connecting lysosomes and mitochondria - a novel role for lipid metabolism in cancer cell death.

Bartel K, Pein H, Popper B, Schmitt S, Janaki-Raman S, Schulze A, Lengauer F, Koeberle A, Werz O, Zischka H, Müller R, Vollmar AM, von Schwarzenberg K.

Cell Commun Signal. 2019 Jul 29;17(1):87. doi: 10.1186/s12964-019-0399-2.


Protective effect of piceatannol and bioactive stilbene derivatives against hypoxia-induced toxicity in H9c2 cardiomyocytes and structural elucidation as 5-LOX inhibitors.

Boccellino M, Donniacuo M, Bruno F, Rinaldi B, Quagliuolo L, Ambruosi M, Pace S, De Rosa M, Olgaç A, Banoglu E, Alessio N, Massa A, Kahn H, Werz O, Fiorentino A, Filosa R.

Eur J Med Chem. 2019 Oct 15;180:637-647. doi: 10.1016/j.ejmech.2019.07.033. Epub 2019 Jul 10.


Liquid chromatography-coupled mass spectrometry analysis of glutathione conjugates of oxygenated polyunsaturated fatty acids.

Liening S, Romp E, Werz O, Scriba GKE, Garscha U.

Prostaglandins Other Lipid Mediat. 2019 Oct;144:106350. doi: 10.1016/j.prostaglandins.2019.106350. Epub 2019 Jul 16.


Vacuolar (H+)-ATPase Critically Regulates Specialized Proresolving Mediator Pathways in Human M2-like Monocyte-Derived Macrophages and Has a Crucial Role in Resolution of Inflammation.

Rao Z, Pace S, Jordan PM, Bilancia R, Troisi F, Börner F, Andreas N, Kamradt T, Menche D, Rossi A, Serhan CN, Gerstmeier J, Werz O.

J Immunol. 2019 Aug 15;203(4):1031-1043. doi: 10.4049/jimmunol.1900236. Epub 2019 Jul 12.


Bioactivity and Mode of Action of Bacterial Tetramic Acids.

Klapper M, Paschold A, Zhang S, Weigel C, Dahse HM, Götze S, Pace S, König S, Rao Z, Reimer L, Werz O, Stallforth P.

ACS Chem Biol. 2019 Aug 16;14(8):1693-1697. doi: 10.1021/acschembio.9b00388. Epub 2019 Jul 11.


The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis.

Nausch B, Pace S, Pein H, Koeberle A, Rossi A, Künstle G, Werz O.

Phytomedicine. 2019 Jul;60:152987. doi: 10.1016/j.phymed.2019.152987. Epub 2019 Jun 10.


The interplay between depression and tuberculosis.

Zhang K, Wang X, Tu J, Rong H, Werz O, Chen X.

J Leukoc Biol. 2019 Sep;106(3):749-757. doi: 10.1002/JLB.MR0119-023R. Epub 2019 Jun 28. Review.


A novel mPGES-1 inhibitor alleviates inflammatory responses by downregulating PGE2 in experimental models.

Lee HH, Moon Y, Shin JS, Lee JH, Kim TW, Jang C, Park C, Lee J, Kim Y, Kim Y, Werz O, Park BY, Lee JY, Lee KT.

Prostaglandins Other Lipid Mediat. 2019 Oct;144:106347. doi: 10.1016/j.prostaglandins.2019.106347. Epub 2019 Jun 20.


An Alternative Pathway to Leukotriene B4 Enantiomers Involving a 1,8-Diol-Forming Reaction of an Algal Oxylipin.

Jagusch H, Werner M, Okuno T, Yokomizo T, Werz O, Pohnert G.

Org Lett. 2019 Jun 21;21(12):4667-4670. doi: 10.1021/acs.orglett.9b01554. Epub 2019 Jun 13.


Melleolides impact fungal translation via elongation factor 2.

Dörfer M, Heine D, König S, Gore S, Werz O, Hertweck C, Gressler M, Hoffmeister D.

Org Biomol Chem. 2019 May 15;17(19):4906-4916. doi: 10.1039/c9ob00562e.


The vitamin E derivative garcinoic acid from Garcinia kola nut seeds attenuates the inflammatory response.

Wallert M, Bauer J, Kluge S, Schmölz L, Chen YC, Ziegler M, Searle AK, Maxones A, Schubert M, Thürmer M, Pein H, Koeberle A, Werz O, Birringer M, Peter K, Lorkowski S.

Redox Biol. 2019 Jun;24:101166. doi: 10.1016/j.redox.2019.101166. Epub 2019 Mar 12.


Novel benzoxanthene lignans that favorably modulate lipid mediator biosynthesis: A promising pharmacological strategy for anti-inflammatory therapy.

Gerstmeier J, Kretzer C, Di Micco S, Miek L, Butschek H, Cantone V, Bilancia R, Rizza R, Troisi F, Cardullo N, Tringali C, Ialenti A, Rossi A, Bifulco G, Werz O, Pace S.

Biochem Pharmacol. 2019 Jul;165:263-274. doi: 10.1016/j.bcp.2019.03.003. Epub 2019 Mar 2.


Discovery of 3-hydroxy-3-pyrrolin-2-one-based mPGES-1 inhibitors using a multi-step virtual screening protocol.

Lauro G, Cantone V, Potenza M, Fischer K, Koeberle A, Werz O, Riccio R, Bifulco G.

Medchemcomm. 2018 Nov 20;9(12):2028-2036. doi: 10.1039/c8md00497h. eCollection 2018 Dec 1.


Gliotoxin from Aspergillus fumigatus Abrogates Leukotriene B4 Formation through Inhibition of Leukotriene A4 Hydrolase.

König S, Pace S, Pein H, Heinekamp T, Kramer J, Romp E, Straßburger M, Troisi F, Proschak A, Dworschak J, Scherlach K, Rossi A, Sautebin L, Haeggström JZ, Hertweck C, Brakhage AA, Gerstmeier J, Proschak E, Werz O.

Cell Chem Biol. 2019 Apr 18;26(4):524-534.e5. doi: 10.1016/j.chembiol.2019.01.001. Epub 2019 Feb 7.


Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome.

Werner M, Jordan PM, Romp E, Czapka A, Rao Z, Kretzer C, Koeberle A, Garscha U, Pace S, Claesson HE, Serhan CN, Werz O, Gerstmeier J.

FASEB J. 2019 May;33(5):6140-6153. doi: 10.1096/fj.201802509R. Epub 2019 Feb 8.


Synthesis, Biological Evaluation and Structure-Activity Relationships of Diflapolin Analogues as Dual sEH/FLAP Inhibitors.

Vieider L, Romp E, Temml V, Fischer J, Kretzer C, Schoenthaler M, Taha A, Hernández-Olmos V, Sturm S, Schuster D, Werz O, Garscha U, Matuszczak B.

ACS Med Chem Lett. 2018 Nov 29;10(1):62-66. doi: 10.1021/acsmedchemlett.8b00415. eCollection 2019 Jan 10.


A Multi-step Virtual Screening Protocol for the Identification of Novel Non-acidic Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) Inhibitors.

Shekfeh S, Çalışkan B, Fischer K, Yalçın T, Garscha U, Werz O, Banoglu E.

ChemMedChem. 2019 Jan 22;14(2):273-281. doi: 10.1002/cmdc.201800701. Epub 2018 Dec 20.


Algal Oxylipins Mediate the Resistance of Diatoms against Algicidal Bacteria.

Meyer N, Rettner J, Werner M, Werz O, Pohnert G.

Mar Drugs. 2018 Dec 4;16(12). pii: E486. doi: 10.3390/md16120486.


Leukotriene-mediated sex dimorphism in murine asthma-like features during allergen sensitization.

Rossi A, Roviezzo F, Sorrentino R, Riemma MA, Cerqua I, Bilancia R, Spaziano G, Troisi F, Pace S, Pinto A, D'Agostino B, Werz O, Cirino G.

Pharmacol Res. 2019 Jan;139:182-190. doi: 10.1016/j.phrs.2018.11.024. Epub 2018 Nov 20.


Melleolides from Honey Mushroom Inhibit 5-Lipoxygenase via Cys159.

König S, Romp E, Krauth V, Rühl M, Dörfer M, Liening S, Hofmann B, Häfner AK, Steinhilber D, Karas M, Garscha U, Hoffmeister D, Werz O.

Cell Chem Biol. 2019 Jan 17;26(1):60-70.e4. doi: 10.1016/j.chembiol.2018.10.010. Epub 2018 Nov 8.


Machine intelligence decrypts β-lapachone as an allosteric 5-lipoxygenase inhibitor.

Rodrigues T, Werner M, Roth J, da Cruz EHG, Marques MC, Akkapeddi P, Lobo SA, Koeberle A, Corzana F, da Silva Júnior EN, Werz O, Bernardes GJL.

Chem Sci. 2018 Jul 17;9(34):6899-6903. doi: 10.1039/c8sc02634c. eCollection 2018 Sep 14.


A 5‑lipoxygenase-specific sequence motif impedes enzyme activity and confers dependence on a partner protein.

Schexnaydre EE, Gerstmeier J, Garscha U, Jordan PM, Werz O, Newcomer ME.

Biochim Biophys Acta Mol Cell Biol Lipids. 2019 Apr;1864(4):543-551. doi: 10.1016/j.bbalip.2018.09.011. Epub 2018 Oct 3.


Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase.

Pein H, Ville A, Pace S, Temml V, Garscha U, Raasch M, Alsabil K, Viault G, Dinh CP, Guilet D, Troisi F, Neukirch K, König S, Bilancia R, Waltenberger B, Stuppner H, Wallert M, Lorkowski S, Weinigel C, Rummler S, Birringer M, Roviezzo F, Sautebin L, Helesbeux JJ, Séraphin D, Mosig AS, Schuster D, Rossi A, Richomme P, Werz O, Koeberle A.

Nat Commun. 2018 Sep 20;9(1):3834. doi: 10.1038/s41467-018-06158-5.


Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity.

Fettel J, Kühn B, Guillen NA, Sürün D, Peters M, Bauer R, Angioni C, Geisslinger G, Schnütgen F, Meyer Zu Heringdorf D, Werz O, Meybohm P, Zacharowski K, Steinhilber D, Roos J, Maier TJ.

FASEB J. 2019 Feb;33(2):1711-1726. doi: 10.1096/fj.201800221R. Epub 2018 Sep 6.


Discovery of a benzenesulfonamide-based dual inhibitor of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase that favorably modulates lipid mediator biosynthesis in inflammation.

Cheung SY, Werner M, Esposito L, Troisi F, Cantone V, Liening S, König S, Gerstmeier J, Koeberle A, Bilancia R, Rizza R, Rossi A, Roviezzo F, Temml V, Schuster D, Stuppner H, Schubert-Zsilavecz M, Werz O, Hanke T, Pace S.

Eur J Med Chem. 2018 Aug 5;156:815-830. doi: 10.1016/j.ejmech.2018.07.031. Epub 2018 Jul 25.


Structural insight into the optimization of ethyl 5-hydroxybenzo[g]indol-3-carboxylates and their bioisosteric analogues as 5-LO/m-PGES-1 dual inhibitors able to suppress inflammation.

Bruno F, Errico S, Pace S, Nawrozkij MB, Mkrtchyan AS, Guida F, Maisto R, Olgaç A, D'Amico M, Maione S, De Rosa M, Banoglu E, Werz O, Fiorentino A, Filosa R.

Eur J Med Chem. 2018 Jul 15;155:946-960. doi: 10.1016/j.ejmech.2018.05.041. Epub 2018 May 28.


Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans.

Guo H, Benndorf R, König S, Leichnitz D, Weigel C, Peschel G, Berthel P, Kaiser M, Steinbeck C, Werz O, Poulsen M, Beemelmanns C.

Chemistry. 2018 Aug 6;24(44):11319-11324. doi: 10.1002/chem.201802066. Epub 2018 Jul 16.


Protective Effect of Casperome®, an Orally Bioavailable Frankincense Extract, on Lipopolysaccharide- Induced Systemic Inflammation in Mice.

Loeser K, Seemann S, König S, Lenhardt I, Abdel-Tawab M, Koeberle A, Werz O, Lupp A.

Front Pharmacol. 2018 Apr 20;9:387. doi: 10.3389/fphar.2018.00387. eCollection 2018.


Lipophilic extracts of Leucas zeylanica, a multi-purpose medicinal plant in the tropics, inhibit key enzymes involved in inflammation and gout.

Napagoda M, Gerstmeier J, Butschek H, Lorenz S, Kanatiwela D, Qader M, Nagahawatte A, De Soyza S, Wijayaratne GB, Svatoš A, Jayasinghe L, Koeberle A, Werz O.

J Ethnopharmacol. 2018 Oct 5;224:474-481. doi: 10.1016/j.jep.2018.04.042. Epub 2018 May 1.


Identification of multi-target inhibitors of leukotriene and prostaglandin E2 biosynthesis by structural tuning of the FLAP inhibitor BRP-7.

Gür ZT, Çalışkan B, Garscha U, Olgaç A, Schubert US, Gerstmeier J, Werz O, Banoglu E.

Eur J Med Chem. 2018 Apr 25;150:876-899. doi: 10.1016/j.ejmech.2018.03.045. Epub 2018 Mar 17.


Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G.

Koeberle A, Henkel A, Verhoff M, Tausch L, König S, Fischer D, Kather N, Seitz S, Paul M, Jauch J, Werz O.

Molecules. 2018 Feb 24;23(2). pii: E506. doi: 10.3390/molecules23020506.


Natural products as inhibitors of prostaglandin E2 and pro-inflammatory 5-lipoxygenase-derived lipid mediator biosynthesis.

Koeberle A, Werz O.

Biotechnol Adv. 2018 Nov 1;36(6):1709-1723. doi: 10.1016/j.biotechadv.2018.02.010. Epub 2018 Feb 15. Review.


Human macrophages differentially produce specific resolvin or leukotriene signals that depend on bacterial pathogenicity.

Werz O, Gerstmeier J, Libreros S, De la Rosa X, Werner M, Norris PC, Chiang N, Serhan CN.

Nat Commun. 2018 Jan 4;9(1):59. doi: 10.1038/s41467-017-02538-5.


A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial).

Stürner KH, Stellmann JP, Dörr J, Paul F, Friede T, Schammler S, Reinhardt S, Gellissen S, Weissflog G, Faizy TD, Werz O, Fleischer S, Vaas LAI, Herrmann F, Pless O, Martin R, Heesen C.

J Neurol Neurosurg Psychiatry. 2018 Apr;89(4):330-338. doi: 10.1136/jnnp-2017-317101. Epub 2017 Dec 16.


Acetyl-CoA carboxylase 1 regulates endothelial cell migration by shifting the phospholipid composition.

Glatzel DK, Koeberle A, Pein H, Löser K, Stark A, Keksel N, Werz O, Müller R, Bischoff I, Fürst R.

J Lipid Res. 2018 Feb;59(2):298-311. doi: 10.1194/jlr.M080101. Epub 2017 Dec 5.

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