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Success Stories Publications Publications Archive	References » Publications Archive Publications Archive 2010 ⇓ Lübberstedt M, Müller-Vieira U, Mayer M, Biemel KM, Knöspel F, Knobeloch D, Nüssler AK, Gerlach JC, Zeilinger K. HepaRG human hepatic cell line utility as a surrogate for primary human hepatocytes in drug metabolism assessment in vitro. J Pharmacol Toxicol Methods. 2010 May 9. 2009 ⇓ Woyda K, Koebrich S, Reiss I, Rudloff S, Pullamsetti SS, Rühlmann A, Weissmann N, Ghofrani HA, Günther A, Seeger W, Grimminger F, Morty RE, Schermuly RT. Inhibition of phosphodiesterase 4 enhances lung alveolarisation in neonatal mice exposed to hyperoxia. Eur Respir J. 2009 Apr;33(4):861-70. S. Koebrich, N. Kinsinger, B. Leiner, L. Hurst, B. Birk, P. Ehmer, C. Batzl-Hartmann Serial blood sampling in hamsters and guinea pigs by catheterization of jugular vein reduces animal numbers in pharmacological studies. Poster - 47. Wissenschafliche Tagung der Gesellschaft für Versuchstierkunde GV-SOLAS und 11. Fortbildungsveranstaltung der IGTp - 13. - 15. September 2009, Wien. Bey E, Marchais-Oberwinkler S, Negri M, Kruchten P, Oster A, Klein T, Spadaro A, Werth R, Frotscher M, Birk B, Hartmann RW. New Insights into the SAR and Binding Modes of Bis(hydroxyphenyl)thiophenes and -benzenes: Influence of Additional Substituents on 17beta-Hydroxysteroid Dehydrogenase Type 1 (17beta-HSD1) Inhibitory Activity and Selectivity. J Med Chem. 2009 Oct 15. Miranda JP, Leite SB, Muller-Vieira U, Rodrigues A, Carrondo MJ, Alves PM. Towards an extended functional hepatocyte in vitro culture. Tissue Eng Part C Methods. 2009 Jun;15(2):157-67. Ries C, Lucas S, Heim R, Birk B, Hartmann RW. Selective aldosterone synthase inhibitors reduce aldosterone formation in vitro and in vivo. J Steroid Biochem Mol Biol. 2009 May 7. Banerjee S, Zvelebil M, Furet P, Mueller-Vieira U, Evans DB, Dowsett M, Martin LA. The Vascular Endothelial Growth Factor Receptor Inhibitor PTK787/ZK222584 Inhibits Aromatase. Cancer Res. 2009 Jun 1;69(11):4716-23. Beckers S, Noor F, Müller-Vieira U, Mayer M, Strigun A, Heinzle E. High throughput, non-invasive and dynamic toxicity screening on adherent cells using respiratory measurements. Toxicol In Vitro. 2009 May 8. Hille UE, Hu Q, Vock C, Negri M, Bartels M, Müller-Vieira U, Lauterbach T, Hartmann RW. Novel CYP17 inhibitors: synthesis, biological evaluation, structure-activity relationships and modelling of methoxy- and hydroxy-substituted methyleneimidazolyl biphenyls. Eur J Med Chem. 2009 Jul;44(7):2765-75. Noor F, Niklas J, Müller-Vieira U, Heinzle E. An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells. Toxicol Appl Pharmacol. 2009 Jun 1;237(2):221-31. 2008 ⇓ Dumitrascu R, Koebrich S, Dony E, Weissmann N, Savai R, Pullamsetti SS, Ghofrani HA, Samidurai A, Traupe H, Seeger W, Grimminger F, Schermuly RT. Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury. BMC Pulm Med. 2008 Dec 17;8:25. Lucas S, Heim R, Ries C, Schewe KE, Birk B, Hartmann RW. In vivo active aldosterone synthase inhibitors with improved selectivity: lead optimization providing a series of pyridine substituted 3,4-dihydro-1H-quinolin-2-one derivatives. J Med Chem. 2008 Dec 25;51(24):8077-87. Bey E, Marchais-Oberwinkler S, Werth R, Negri M, Al-Soud YA, Kruchten P, Oster A, Frotscher M, Birk B, Hartmann RW. Design, synthesis, biological evaluation and pharmacokinetics of bis(hydroxyphenyl) substituted azoles, thiophenes, benzenes, and aza-benzenes as potent and selective nonsteroidal inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1). J Med Chem. 2008 Nov 13;51(21):6725-39. Pinto-Bazurco Mendieta MA, Negri M, Hu Q, Hille UE, Jagusch C, Jahn-Hoffmann K, Müller-Vieira U, Schmidt D, Lauterbach T, Hartmann RW. CYP17 inhibitors. Annulations of additional rings in methylene imidazole substituted biphenyls: synthesis, biological evaluation and molecular modelling. Arch Pharm (Weinheim). 2008 Oct;341(10):597-609. Hu Q, Negri M, Jahn-Hoffmann K, Zhuang Y, Olgen S, Bartels M, Müller-Vieira U, Lauterbach T, Hartmann RW. Synthesis, biological evaluation, and molecular modeling studies of methylene imidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17)--part II: Core rigidification and influence of substituents at the methylene bridge. Bioorg Med Chem. 2008 Aug 15;16(16):7715-27. Pinto-Bazurco Mendieta MA, Negri M, Jagusch C, Müller-Vieira U, Lauterbach T, Hartmann RW. Synthesis, biological evaluation, and molecular modeling of abiraterone analogues: novel CYP17 inhibitors for the treatment of prostate cancer. J Med Chem. 2008 Aug 28;51(16):5009-18. Sandrine Marchais-Oberwinkler, Patricia Kruchten, Martin Frotscher, Erika Ziegler, Alexander Neugebauer, Umadevi Bhoga, Emmanuel Bey, Ursula Müller-Vieira, Josef Messinger, Hubert Thole and Rolf W. Hartmann. Substituted 6-Phenyl-2-naphthols. Potent and Selective Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1): Design, Synthesis, Biological Evaluation, and Pharmacokinetics. J. Med. Chem., 51 (15), 4685–4698, 2008. Ralf Heim, Simon Lucas, Cornelia M.Grombein, Christina Ries, Katarzyna E. Schewe, Matthias Negri, Ursula Müller-Vieira, Barbara Birk and Rolf W. Hartmann. Overcoming Undesirable CYP1A2 Inhibition of Pyridylnaphthalene-Type Aldosterone Synthase Inhibitors: Influence of Heteroaryl Derivatization on Potency and Selectivity. J. Med. Chem., 51 (16), 5064–5074, 2008. Jagusch C, Negri M, Hille UE, Hu Q, Bartels M, Jahn-Hoffmann K, Mendieta MA, Rodenwaldt B, Müller-Vieira U, Schmidt D, Lauterbach T, Recanatini M, Cavalli A, Hartmann RW. Synthesis, biological evaluation and molecular modelling studies of methyleneimidazole substituted biaryls as inhibitors of human 17alpha-hydroxylase-17,20-lyase (CYP17). Part I: Heterocyclic modifications of the core structure. Bioorg. Med. Chem;16,1992-2010, 2008 Frotscher M, Ziegler E, Marchais-Oberwinkler S, Kruchten P, Neugebauer A, Fetzer L, Scherer C, Müller-Vieira U, Messinger J, Thole H and Hartmann RW. Design, Synthesis, and Biological Evaluation of (Hydroxyphenyl)naphthalene and -quinoline Derivatives: Potent and Selective Nonsteroidal Inhibitors of 17β-Hydroxysteroid Dehydrogenase Type 1 (17β-HSD1) for the Treatment of Estrogen-Dependent Diseases. J. Med. Chem., 51, 2158-2169, 2008 Pinto-Bazurco Mendieta MA, Negri M, Jagusch C, Hille UE, Müller-Vieira U, Schmidt D, Hansen K, Hartmann RW. Synthesis, biological evaluation and molecular modelling studies of novel ACD- and ABD-ring steroidomimetics as inhibitors of CYP17. Bioorg Med Chem Lett. 2008 Jan 1;18(1):267-73 2007 ⇓ B Rodenwaldt, K M Biemel, L Hurst, P Ehmer and C Batzl-Hartmann Determination of drug pharmacokinetics by means of cassette dosing and cassette analysing: a time- and cost-saving drug screening approach that also reduces animal use Proceedings of the Tenth Felasa Symposium and the XIV ICLAS General Assembly & Conference - Cernobbio, Italy. 11-14 June 2007 Rodenwaldt B, Pohl U, de Wit C. Endogenous and exogenous NO attenuates the conduction of vasoconstrictions along arterioles in the microcirculation. Am J Physiol Heart Circ Physiol 292 (2007): H2341–H2348 2006 ⇓ Müller-Vieira U. Optimized Human Hepatic in vitro Models. Reducing Animal Experimentation in Preclinical Predictive Drug Testing. BIOforum Europe 12 (2006); 40-41 Voets M., Antes I., Scherer C., Müller-Vieira U., Biemel K., Marchais-Oberwinkler S., Hartmann RW. Synthesis and evaluation of heteroaryl-substituted dihydronaphthalenes and indenes: potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. J. Med. Chem. 49 (2006) 2222-2231 Salem OI, Frotscher M, Scherer C, Neugebauer A, Biemel K, Streiber M, Maas R, Hartmann RW. Novel 5alpha-reductase inhibitors: synthesis, structure-activity studies, and pharmacokinetic profile of phenoxybenzoylphenyl acetic acids. J Med Chem. 2006 Jan 26;49(2):748-59 2005 ⇓ Y. Braun, D. H. Wai, K. Biemel, K.-L. Schäfer, H. E. Gabbert, C. Poremba Biochip Analys: Statutus Quo / Biochip-Analyse: Eine Standortbestimmung. Verh. Dtsch. Ges. Path. 89, 116-124 (2005) Ulmschneider S., Müller-Vieira U., Mitrenga M., Hartmann R. W., Oberwinkler-Marchais S., Klein C. D., Bureik M., Bernhardt R., Antes I., Lengauer T. Synthesis and evaluation of imidazolylmethylenetetra-hydronaphthalenes and imidazolylmethyleneindanes: Potent inhibitors of aldosterone synthase. J. Med. Chem. 48 (2005) 1796-1805 Ulmschneider S., Müller-Vieira U., Klein C. D., Antes, I., Lengauer T., Hartmann R. W. Synthesis and evaluation of pyridylmethylene-tetrahydronaphthalenes/-indanes and structurally modified derivatives: Potent and selective inhibitors of aldosterone synthase (CYP11B2). J. Med. Chem. 48 (2005), 1563-1575 Müller-Vieira U., Angotti M., Hartmann R. W. The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11Beta-hydroxylase) inhibitors. J. Steroid Biochem. Mol. Biol. 96 (2005) 259-270 Voets M., Antes I., Scherer C., Müller-Vieira U., Biemel K., Barassin C., Marchais-Oberwinkler S., Hartmann R. W. Heteroaryl-Substituted Naphthalenes and Structurally Modified Derivatives: Selective Inhibitors of CYP11B2 for the Treatment of Congestive Heart Failure and Myocardial Fibrosis. J. Med. Chem. 48 (2005):6632-6642 Deshpande RR, Koch-Kirsch Y, Maas R , John GT, Krause C, Heinzle E Microplates with integrated oxygen sensors for kinetic cell respiration measurement and cytotoxicity testing in primary and secondary cell lines. Assay Drug Dev Technol. 2005 Jun;3(3):299-307 Bartholomä P, Impidjati, Reininger-Mack A, Zhang Z, Thielecke H, Robitzki A A more aggressive breast cancer spheroid model coupled to an electronic capillary sensor system for a high content screening of cytotoxic agents in cancer therapy. J Biomol Screen 2005 Oct;10(7):705-714 P. Bartholomä, E. Gorjup, D. Monz, A. Reininger-Mack, H. Thielecke, A. Robitzki Three dimensional in vitro reaggregates of embryonic cardiomyocytes: a potential model system for monitoring the heart muscle. J Biomol Screen 2005 Dec;10(8):814-822 Voets M, Antes I, Scherer C, Muller-Vieira U, Biemel K , Barassin C, Marchais-Oberwinkler S, Hartmann RW. Heteroaryl-substituted naphthalenes and structurally modified derivatives: selective inhibitors of CYP11B2 for the treatment of congestive heart failure and myocardial fibrosis. J Med Chem. 2005 Oct 20;48(21):6632-42 V.M. Monnier, G.T. Mustata, K.M. Biemel, O. Reihl, M.O. Lederer, D. Zhenyu, D.R. Sell Cross-linking of the extracellular matrix by the maillard reaction in aging and diabetes: an update on "a puzzle nearing resolution".Proceedings of the 8th International Symposium on the Maillard Reaction, 2005, NYAS. Ann N Y Acad Sci. 2005 Jun;1043:533-44. Review G.T. Mustata, M. Rosca, K.M. Biemel, O. Reihl, M.A. Smith, A. Viswanathan, C. Strauch, Y. Du, J. Tang, T.S. Kern, M.O. Lederer, M. Brownlee, M.F. Weiss, V.M. Monnier Paradoxical effects of green tea (camellia sinensis) and antioxidant vitamins in diabetic rats: improved retinopathy and renal mitochondrial defects but deterioration of collagen matrix glycoxidation and cross-linking Diabetes 2005, 54(2), 517-526. D.R. Sell, K.M. Biemel, O. Reihl, M.O. Lederer, C.M. Strauch, and V.M. Monnier Glucosepane is a major protein cross-link of the senescent human extracellular matrix. Relationship with diabetes J. Biol. Chem. 2005, 280(13), 12310-12315. 2004 ⇓ Voets M., Müller-Vieira U., Marchais-Oberwinkler S., Hartmann R. W Synthesis of amidinohydrazones and evaluation of their inhibitory effect towards aldosterone synthase (CYP11B2) and the formation of selected steroids. Arch. Pharm. Pharm. Med. Chem. 337 (2004) 411-416 Schertl S, Hartmann RW, Batzl-Hartmann C, Bernhardt G, Spruss T, Beckenlehner K, Koch M, Krauser R, Schlemmer R, Gust R, Schonenberger H [1, 2-Bis(2, 6-difluoro-3-hydroxyphenyl)ethylene-diamine]platinum(II) complexes, compounds for the endocrine therapy of breast cancer - mode of action II: contribution of drug inactivation, cellular drug uptake and sterical factors in the drug-target interaction to the antitumor activity. Arch Pharm (Weinheim). 2004 Jun;337(6):349-59 Schertl S, Hartmann RW, Batzl-Hartmann C, Bernhardt G, Spruss T, Beckenlehner K, Koch M, Krauser R, Schlemmer R, Gust R, Schonenberger H. [1, 2-Bis(2, 6-difluoro-3-hydroxyphenyl)ethylene-diamine]platinum(II) complexes, compounds for the endocrine therapy of breast cancer - mode of action I: antitumor activity due to the reduction of the endogenous estrogen level. Arch Pharm (Weinheim). 2004 Jun;337(6):335-48. T. Mitschele, B. Diesel, M. Friedrich, V. Meineke, R.M. Maas, B.C. Gartner, J. Kamradt, E. Meese, W. Tilgen, J. Reichrath Analysis of vitamin D system in basal cell carcinomas (BCCs) Lab. Invest. 2004, 84(6), 693-702. O. Reihl, K.M. Biemel, M.O. Lederer, W. Schwack Pyridinium carbaldehyde: Active Maillard reaction product from the reaction of hexoses with lysine residues Carbohydr. Res. 2004, 339(9), 1609-1618 E. Heinzle, R. Deshpande, U. Bock, G. John, C. Krause, G. Müller, H. Waltenberger, R.M. Maas Entwicklung von innovativen Miktrotiterplattenreaktoren zur Bewertung des Abbaus und der Toxizität neuer Wirkstoffe auf Basis von Mikrosomen und Säugerzellen transkript 2004, Sonderband Biokatalyse, 66-67. 2003 ⇓ Hartmann R. W., Müller U., Ehmer P. B. Discovery of selective CYP11B2 (aldosterone synthase) inhibitors for the therapy of congestive heart failure and myocardial fibrosis. Eur. J. Med. Chem. 38 (2003) 363-366 C. Batzl-Hartmann, D.B. Evans and A.S. Bhatnagar Comparative aromatase enzyme kinetic studies on fadrozole, formestane, letrozole, anastrozole and exemestane Proc. AACR 44 2003, Abstract 539, p123. S. Haidar, P. Ehmer, S. Barassin, C. Batzl-Hartmann, R.W. Hartmann Effects of novel 17alpha-hydroxylase/C17, 20-lyase (P450 17, Cyp17) inhibitors on androgen biosynthesis in vitro and in vivo J. Steroid. Biochem. Mol. Biol. 2003, 84, 555-562 K.M. Biemel, M.O. Lederer Site-specific quantitative evaluation of the protein glycation product N6-(2,3-dihydroxy-5,6-dioxohexyl) -L-lysinate by LC-(ESI)MS peptide mapping: Evidence for its key role in AGE formation Bioconjugate Chem. 2003, 14(3), 619-628 O.Reihl, K.M. Biemel, W. Eipper, M.O. Lederer, W. Schwack Spiro cross-links: Representatives of a new class of glycoxidation products J. Agric. Food Chem. 2003, 51(16), 4810-4818 2002 ⇓ Bartholoma, P., Erlandsson, N., Kaufmann, K., Rossler, O.G., Baumann, B., Wirth, T., Giehl, K.M. and Thiel, G Neuronal cell death induced by antidepressants: lack of correlation with Egr-1, NF-kappa B and extracellular signal-regulated protein kinase activation. Biochem Pharmacol (2002); 63: 1507-1516 Ehmer P. B., Bureik M., Bernhardt R., Müller U., Hartmann R. W. Development of a test system for inhibitors of human aldosterone synthase (CYP11B2): screening in fission yeast and evaluation of selectivity in V79 cells. J. Steroid Biochem. Mol. Biol. 81 (2002) 173-179 Hoepfl B, Rodenwaldt B, Pohl U, De Wit C. EDHF, but not NO or prostaglandins, is critical to evoke a conducted dilation upon ACh in hamster arterioles. Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H996-H1004.PMID: 12181129 F. Picard, S. Barassin, A. Mokhtarian, R.W. Hartmann Synthesis and evaluation of 2'-substituted 4-(4'-carboxy- or 4'-carboxymethylbenzylidene)-N-acylpiperidines: highly potent and in vivo active steroid 5alpha-reductase type 2 inhibitors J. Med. Chem. 2002, 45, 3406 K.M. Biemel, D.A. Friedl, M.O. Lederer Identification and quantification of major Maillard-crosslinks in human serum albumin and lens protein: Evidence for glucosepane as the dominant compound J. Biol. Chem. 2002, 277, 24907-24915 K.M. Biemel, J. Conrad, M.O. Lederer Unexpected carbonyl mobility in aminoketoses: The key to major Maillard crosslinks Angew. Chem. Int. Ed. Engl. 2002, 41, 801-804 R.H. Nagaraj, P.Sarkar, A. Mally, K.M. Biemel, M.O. Lederer, P.S. Padayatti Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: Characterization of a major product from the reaction of pyridoxamine and methylglyoxal Arch. Biochem. Biophys. 2002, 402, 110-119 K.M. Biemel, O. Reihl, J. Conrad, M.O. Lederer Formation pathways for lysine-arginine cross-links derived from hexoses and pentoses by Maillard processes Proceedings of the 7th International Symposium on the Maillard Reaction-ICS 1245 C 2002, Elsevier, 255-261. 2001 ⇓ S. Schertl, R.W. Hartmann, C. Batzl-Hartmann, R. Schlemmer, T. Spruss, G. Bernhardt, R. Gust, H. Schonenberger 1-(2,6-dichloro-4-hydroxyphenyl)-2-phenylethanes--new biological response modifiers for the therapy of breast cancer. Synthesis and evaluation of estrogenic/antiestrogenic properties Arch Pharm 2001, 334(4), 125-37 K.M. Biemel, O. Reihl, J. Conrad, M.O. Lederer Formation pathways for lysine-arginine cross-links derived from hexoses and pentoses by Maillard processes: Unraveling the structure of a pentosidine precursor J. Biol. Chem. 2001, 276, 23405-23412 A. Munnia, N. Schütz, B.F. Romeike, E. Maldener, B. Glass, R. Maas, W. Nastainczyk, W. Feiden, U. Fischer, E. Meese Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor Oncogene (2001), 20(35), 4853 K.M. Biemel, K.M. Bühler, O. Reihl, M.O. Lederer Identification and quantitative evaluation of the lysine-arginine crosslinks GODIC, MODIC, DODIC, and glucosepane in foods Nahrung/Food 2001, 43, 210-214 2000 ⇓ Ruschitzka FT, Wenger RH, Stallmach T, Quaschning T, de Wit C, Wagner K, Labugger R, Kelm M, Noll G, Rulicke T, Shaw S, Lindberg RL, Rodenwaldt B, Lutz H, Bauer C, Luscher TF, Gassmann M. Nitric oxide prevents cardiovascular disease and determines survival in polyglobulic mice overexpressing erythropoietin. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11609-13. M. Ortmanns, Y. Manoli, F. Gerfers, A. Michel, E. Meese, R.M. Maas Direkte Detektion hybridisierter DNA auf der Oberfläche mikroelektronischer Chips "BIONA-report 14", EDS. A. Wisser, W. Nachtigall, Akad. Wiss. Lit., Mainz, 2000, 184-187. R.M. Maas, K. Reus, B. Diesel, W.I. Steudel, W. Feiden, U. Fischer, E. Meese Amplification and expression of splice variants of the gene encoding the P450 cytochrome 25-hydroxyvitamin D(3) 1,alpha-hydroxylase (CYP 27B1) in human malignant glioma Clin Cancer Res. 2000 7(4), 868-875 1998 ⇓ R.M. Maas, J. Götz, W. Wohlleben, G. Muth The conjugative plasmid pSG5 from Streptomyces ghanaensis DSM 2932 differs in its transfer functions from other Streptomyces rolling-circle-type plasmids Microbiology 1998, 144, 2809-2817 L. Criscione, P. Rigollier, C. Batzl-Hartmann, H. Rueger, A. Stricker-Krongrad, P. Wyss et al Food intake in free-feeding and energy-deprived lean rats is mediated by the neuropeptide Y5 receptor J. Clin. Invest. 1998, 12, 2136 1997 ⇓ R. Maas, I. Ersfeld, G. Muth, W. Wohlleben Complete nucleotide sequence of the temperature-sensitive plasmid pSG5 from Streptomyces ghanaensis. 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