Group of Prof. Daniel Merk - Faculty for Chemistry and Pharmacy
Group of Prof. Daniel Merk - Faculty for Chemistry and Pharmacy
(125) Lewandowski, M.; Carmina, M.; Knümann, L.; Sai, M.; Willems, S.; Kasch, T.; Pollinger, J.; Knapp, S.; Marschner, J. A.; Chaikuad, A.; Merk, D. Structure-Guided Design of a Highly Potent Partial RXR Agonist with Superior Physicochemical Properties. J. Med. Chem., 2024, DOI: 10.1021/acs.jmedchem.3c02095.
(124) Isigkeit, L.; Kärcher, A.; Adouvi, G.; Arifi, S.; Merk, D. Rational design and virtual screening identify mimetics of the RXR agonist valerenic acid. ChemMedChem, 2024, DOI: 10.1002/cmdc.202300379.
(123) Hye Khan, A.; Nolan, B.; Stavniichuk, A.; Merk, D.; Imig, J. D. Dual Soluble Epoxide Hydrolase Inhibitor – Farnesoid X Receptor Agonist Interventional Treatment Attenuates Renal Inflammation and Fibrosis. Front. Immunol., 2023, 14, 1269261.
(122) Adouvi, G.; Nawa, F.; Ballarotto, M.; Rüger, L. A.; Knümann, L.; Kasch, T.; Arifi, S.; Schubert-Zsilavecz, M.; Willems, S.; Marschner, J. A.; Pabel, J.; Merk, D. Structural Fusion of Natural and Synthetic Ligand Features Boosts RXR Agonist Potency. J. Med. Chem., 2023, 66, 16762–16771.
(121) Stiller, T.; Merk, D. Exploring Fatty Acid Mimetics as NR4A Ligands. J. Med. Chem., 2023, 66, 15362–15369.
(120) Sai, M.; Vietor, J.; Kornmayer, M.; Egner, M.; López-García, U.; Höfner, G.; Pabel, J.; Marschner, J.; Wein, T.; Merk, D. Structure-Guided Design of Nurr1 Agonists Derived from the Natural Ligand Dihydroxyindole. J. Med. Chem., 2023, 13556–13567.
(119) Zaienne, D.; Isigkeit, L.; Marschner, J.; Duensing-Kropp, S.; Höfner, G.; Merk, D. Structural Modification of the Natural Product Valerenic Acid Tunes RXR Homodimer Agonism. ChemMedChem, 2023, 18, e202300404.
(118) Rao, Z.; Brunner, E.; Giszas, B.; Iyer-Bierhoff, A.; Gerstmeier, J.; Börner, F.; Jordan, P.; Pace, S.; Meyer, K.; Hofstetter, R.; Merk, D.; Paulenz, C.; Heinzel, T.; Grunert, P.; Stallmach, A.; Serhan, C.; Werner, M.; Werz, O. Glucocorticoids regulate lipid mediator networks by reciprocal modulation of 15-lipoxygenase isoforms affecting inflammation resolution. Proc. Nat. Acad. Sci. U.S.A., 2023, 120(35), e2302070120.
(117) Schallmayer, E.; Merk, D. A Fluorescence-Based Reporter Gene Assay to Characterize Nuclear Receptor Modulators. Methods Mol Biol., 2023, 2706, 125-135.
(116) Isigkeit, L.; Merk, D. Compilation of Custom Compound/Bioactivity Datasets from Public Repositories. Methods Mol Biol., 2023, 2706, 25-50.
(115) Chaikuad, A.; Merk, D. An Introduction to Chemogenomics. Methods Mol Biol., 2023, 2706, 1-10.
(114) Arifi, S.; Marschner, J.; Pollinger, J.; Isigkeit, L.; Heitel, P.; Kaiser, A.; Obeser, L.; Höfner, G.; Proschak, E.; Knapp, S.; Chaikuad, A.; Heering, J.; Merk, D. Targeting the Alternative Vitamin E Metabolite Binding Site Enables Noncanonical PPARγ Modulation. J. Am. Chem. Soc., 2023, 145(27), 14802–14810.
(113) Ballarotto, M.; Willems, S.; Stiller, T.; Nawa, F.; Marschner, J.; Grisoni, F.; Merk, D. De Novo Design of Nurr1 Agonists via Fragment-Augmented Generative Deep Learning in Low-Data Regime. J. Med. Chem., 2023, 66, 8170–8177.
(112) Vietor, J.; Gege, C.; Stiller, T.; Busch, R.; Schallmayer, E.; Kohlhof, H.; Höfner, G.; Pabel, J.; Marschner, J.; Merk, D. Development of a Potent Nurr1 Agonist Tool for In Vivo Applications. J. Med. Chem., 2023, 66, 6391–6402.
(111) Isigkeit, L.; Merk, D. Opportunities and Challenges in Targeting Orphan Nuclear Receptors. Chem. Commun., 2023, 59, 4551–4561.
(110) Mukhopadhyay, T.; Willems, S.; Arp, C.; Morstein, J.; Haake, C.; Merk, D.; Trauner, D. Development of Light Activated LXR Agonists. ChemMedChem, 2023, 18, e2022006.
(109) Adouvi, G.; Isigkeit, L.; Lopez, Ú; Marschner, J.; Schubert-Zsilavecz, M.; Merk, D. Rational design of a new RXR agonist scaffold enabling single-subtype preference for RXRα, RXRβ and RXRγ. J. Med. Chem., 2023, 66, 333–344.
(108) Bohn, T.; de Lera, A.; Landrier, J.-F.; Carlsen, H.; Merk, D.; Todt, T.; Renaut, J.; Rühl, R. Methodological state-of-the-art of carotenoid studies - from organic synthesis via metabolism to bioactive carotenoid metabolites and assessing their biological activity to result evaluation – as exemplified by a novel retinoid signalling pathway. Food Funct., 2023, 14, 621–638.
(107) Steinmetz-Späh, J.; Liu, J.; Singh, R.; Ekoff, M.; Boddul, S.; Tang, X.; Bergqvist, F.; Idborg, H; Heitel, P.; Rönnberg, E.; Merk, D.; Wermeling, F.; Haeggström, J.; Nilsson, G.; Steinhilber, D.; Larsson, K.; Korotkova, M.; Jakobsson, P.-J. Biosynthesis of prostaglandin 15dPGJ2 -glutathione and -cysteine conjugates in macrophages and mast cells via MGST3. J. Lipid Res., 2022, 63, 100310.
(106) Heering, J.; Jores, N.; Kilu, W.; Schallmayer, E.; Peelen, E.; Muehler, A.; Kohlhof, H.; Vitt, D.; Linhard, V.; Gande, S.; Chaikuad, A.; Sreeramulu, S.; Schwalbe, H.; Merk, D. Mechanistic impact of different ligand scaffolds on FXR modulation suggests avenues to selective modulators. ACS Chem. Biol., 2022, 17, 3159–3168.
(105) Arifi, S.; Zaienne, D.; Heering, J.; Wein, T.; Zhubi, R.; Chaikuad, A.; Knapp, S.; Marschner, J.; Merk, D. Fragment-based discovery of orphan nuclear receptor Nur77/NGFI-B ligands. Bioorg. Chem., 2022, 106164.
(104) Helmstädter, M.; Schierle, S.; Isigkeit, L.; Proschak, E.; Marschner, J.; Merk, D. Activity screening of fatty acid mimetic drugs identified nuclear receptor agonists. Int. J. Mol. Sci., 2022, 23, 10070.
(103) Ehrler, J.; Brunst, S.; Tjaden, A.; Kilu, W.; Heering, J.; Hernandez-Olmos, V.; Krommes, A.; Kramer, J.; Steinhilber, D.; Schubert-Zsilavecz, M.; Müller-Knapp, S.; Merk, D.; Proschak, E. Compilation and evaluation of a fatty acid mimetics screening library. Biochem. Pharmacol. 2022, 204, 115191.
(102) Willems S.; Merk, D. Medicinal Chemistry and Chemical Biology of Nurr1 Modulators: An Emerging Strategy in Neurodegeneration. J. Med. Chem., 2022, 65, 9548–9563.
(101) Zaienne, D.; Arifi, S.; Marschner, J.; Heering, J.; Merk, D. Druggability evaluation of the neuron derived orphan receptor (NOR-1) reveals inverse NOR-1 agonists. ChemMedChem, 2022, 17, e202200259.
(100) Willems, S.; Marschner, J.; Kilu, W.; Faudone, G.; Busch, R.; Duensing-Kropp, S.; Heering, J.; Merk, D. Nurr1 modulation mediates neuroprotective effects of statins. Adv. Sci., 2022, 9(18), 2104640.
(99) Isigkeit, L.; Chaikuad, A.; Merk, D. A Consensus Compound/Bioactivity Dataset for Data-Driven Drug Design and Chemogenomics. Molecules, 2022, 27(8), 2513.
(98) Willems, S.; Müller, M.; Ohrndorf, J.; Heering, J.; Proschak, E.; Merk, D. Scaffold hopping from amodiaquine to novel Nurr1 agonist chemotypes via microscale analogue libraries. ChemMedChem, 2022, 17, e202200026.
(97) Faudone, G.; Zhubi, R.; Celik, F.; Knapp, S.; Chaikuad, A.; Heering, J.; Merk, D. Design of a potent TLX agonist by rational fragment fusion. J. Med. Chem., 2022, 65, 2288–2296.
(96) Müller, S.; Ackloo, S.; Al Chawaf, A.; Al-Lazikani, B.; Antolin, A.; Baell, J.; Beck, H.; Beedie, S.; Betz, U.; Bezerra, G.; Brennan, P.; Brown, D.; Brown, P.; Bullock, A.; Carter, A.; Chaikuad, A.; Chaineau, M.; Ciulli, A.; Collins, I.; Dreher, J.; Drewry, D.; Edfeldt, K.; Edwards, A.; Egner, U.; Frye, S.; Fuchs, S.; Hall, M.; Hartung, I.; Hillisch, A.; Hitchcock, S.; Homan, E.; Kannan, N.; Kiefer, J.; Knapp, S.; Kostic, M.; Kubicek, S.; Leach, A.; Lindemann, S.; Marsden, B.; Matsui, H.; Meier, J.; Merk, D.; Michel, M.; Morgan, M.; Mueller-Fahrnow, A.; Owen, D.; Perry, B.; Rosenberg, S.; Saikatendu, K.; Schapira, M.; Scholten, C.; Sharma, S.; Simeonov, A.; Sundström, M.; Superti-Furga, G.; Todd, M.; Tredup, C.; Vedadi, M.; von Delft, F.; Willson, T.; Winter, G.; Workman, P.; Arrowsmith, C. Target 2035 – update on the quest for a probe for every protein. RSC Med. Chem., 2021, 13, 13–21.
(95) Lang, A.; Isigkeit, L.; Schubert-Zsilavecz, M.; Merk, D. The Medicinal Chemistry and Therapeutic Potential of LRH-1 Modulators. J. Med. Chem., 2021, 64, 16956–16973.
(94) Faudone, G.; Kilu, W.; Ni, X.; Chaikuad, A.; Sreeramulu, S.; Heitel, P.; Schwalbe, H.; Knapp, S.; Schubert-Zsilavecz, M.; Heering, J.; Merk, D. The Transcriptional Repressor Orphan Nuclear Receptor TLX Is Responsive To Xanthines. ACS Pharmacol. Transl. Sci., 2021, 4, 1794–1807.
(93) Lillich, F.; Willems, S.; Ni, X.; Borkowsky, C.; Kilu, W.; Brodsky, M.; Kramer, J.; Brunst, S.; Hernandez-Olmos, V.; Heering, J.; Schierle, S.; Kestner, R.; Mayser, F.; Helmstädter, M.; Göbel, T.; Weizel, L.; Namgaladze, D.; Kaiser, A.; Steinhilber, D.; Pfeilschifter, W.; Kahnt, A.; Proschak, A.; Chaikuad, A.; Knapp, S.; Merk, D.; Proschak, E. Structure-Based Design of Dual Partial Peroxisome Proliferator-Activated Receptor γ Agonists/ Soluble Epoxide Hydrolase Inhibitors. J. Med. Chem., 2021, 64, 17259–17276.
(92) Zaienne, D.; Willems, S.; Schierle, S.; Heering, J.; Merk, D. Development and Profiling of Inverse Agonist Tools for the Neuroprotective Transcription Factor Nurr1. J. Med. Chem., 2021, 64, 15126–15140.
(91) Imig, J.; Merk, D.; Proschak, E. Multi-Target Drugs for Kidney Diseases. Kidney360, 2021, 2(10), 1645–1653.
(90) Yu, O.; Webb, D.; Di Milo, E.; Mutchie, T.; Teske, K.; Chen, T.; Lin, W.; Peluso-Iltisc, C.; Rochel, N.; Helmstädter, M.; Merk, D.; Arnold, L. Biological Evaluation and Synthesis of Calcitroic Acid. Bioorg. Chem., 2021, 116, 105310.
(89) Moret, M.; Helmstädter, M.; Grisoni, F.; Schneider, G.; Merk, D. Beam search for automated design and scoring of novel ROR ligands with machine intelligence. Angew. Chem. Int. Ed., 2021, 60, 19477–19482.
Moret, M.; Helmstädter, M.; Grisoni, F.; Schneider, G.; Merk, D. Beam-Search zum automatisierten Entwurf und Scoring neuer ROR-Liganden mithilfe maschineller Intelligenz. Angew. Chem., 2021, DOI: 10.1002/ange.202104405.
(88) Willems, S.; Zaienne, D.; Merk, D. Targeting nuclear receptors in neurodegeneration and neuroinflammation. J. Med. Chem., 2021, 64, 9592–9638.
(87) Willems, S.; Morstein, J.; Hinnah, K.; Trauner, D.; Merk, D. A Photohormone for Light-dependent Control of PPARα in Live Cells. J. Med. Chem., 2021, 64, 10393–10402.
(86) Helmstädter, M.; Kaiser, A.; Brunst, S.; Schmidt, J.; Ronchetti, R.; Weizel, L.; Proschak, E.; Merk, D. Second-generation dual FXR/sEH modulators with optimized pharmacokinetics. J. Med. Chem., 2021, 64, 9525–9536.
(85) Grisoni, F.; Huisman, B.; Button, A.; Moret, M.; Atz, K.; Merk, D.; Schneider, G. Combining generative artificial intelligence and on-chip synthesis for de novo drug design. Sci. Adv., 2021, 7, eabg3338.
(84) Faudone, G.; Bischoff-Kont, I.; Rachor, L.; Willems, S.; Zhubi, R.; Kaiser, A.; Chaikuad, A.; Knapp, S.; Fürst, R.; Heering, J.; Merk, D. Propranolol activates the orphan nuclear receptor TLX to counteract proliferation and migration of glioblastoma cells. J. Med. Chem., 2021, 64, 8727–8738.
(83) Kilu, W.; Merk, D.; Steinhilber, D.; Proschak, E.; Heering, J. Heterodimer formation with retinoic acid receptor RXRα modulates coactivator recruitment by peroxisome proliferator-activated receptor PPARγ. J. Biol. Chem., 2021, 297, 100814.
(82) Friedrich, L.; Cingolani, G.; Ko, Y.-H; Iaselli, M.; Miciaccia, M.; Perrone, M. G.; Neukirch, K.; Bobinger, V.; Merk, D.; Werz, O.; Koeberle A.; Scilimati, A.; Schneider, G. From a marine natural product to synthetic cyclooxygenase-1 inhibitors using machine intelligence. Adv. Sci., 2021, 2100832.
(81) Willems, S.; Gellrich, L.; Chaikuad, A.; Kluge, S.; Werz, O.; Heering, J.; Knapp, S.; Lorkowski, S.; Schubert-Zsilavecz, M.; Merk, D. Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions. Cell Chem. Biol., 2021, 28, 1489–1500.
(80) Faudone, G.; Arifi, S.; Merk, D. The Medicinal Chemistry of Caffeine. J. Med. Chem., 2021, 64, 7156–7178.
(79) Schierle, S.; Brunst, S.; Helmstädter, M.; Ebert, R.; Kramer, J.; Steinhilber, D.; Proschak, E.; Merk, D. Development and in vitro profiling of dual FXR/LTA4H modulators. ChemMedChem, 2021, 16, 2366–2374.
(78) Schierle, S.; Chaikuad, A.; Lillich, F.; Ni, X.; Woltersdorf, S.; Schallmayer, E.; Renelt, B.; Ronchetti, R.; Knapp, S.; Proschak, E.; Merk, D. Oxaprozin analogues as selective RXR agonists with superior properties and pharmacokinetics. J. Med. Chem., 2021, 64, 5123–5136.
(77) Helmstädter, M.; Schmidt, J.; Kaiser, A.; Weizel, L.; Proschak, E.; Merk, D. Differential therapeutic effects of FXR activation, sEH inhibition and dual FXR/sEH modulation in NASH in diet-induced obese mice. ACS Pharmacol. Transl. Sci., 2021, 4, 966–979.
(76) Ni, X.; Schröder, M.; Olieric, V.; Sharpe, M. E.; Merk, D.; Knapp, S.; Chaikuad, A. Structural insights into plasticity and discovery of remdesivir metabolite GS-441524 binding in SARS-CoV-2 macrodomain. ACS Med. Chem. Lett., 2021, 12, 603–609.
(75) Willems, S.; Ohrndorf, J.; Kilu, W.; Heering, J.; Merk, D. Fragment-like chloroquinolineamines activate the orphan nuclear receptor Nurr1 and elucidate activation mechanisms. J. Med. Chem., 2021, 64, 2659–2668.
(74) Hartmann, M.; Bibli, S.-I.; Tews, D.; Ni, X.; Kircher, T.; Kramer, J.; Kilu, W.; Heering, J.; Hernandez Olmos, V.; Weizel, L.; Scriba, G.; Krait, S.; Knapp, S.; Chaikuad, A.; Merk, D.; Fleming, I.; Fischer-Posovszky, P.; Proschak, E. Combined cardioprotective and adipocyte browning effects promoted by the eutomer of dual sEH/PPARγ modulator. J. Med. Chem., 2021, 64, 2815–2828.
(73) Helmstädter, M.; Vietor, J.; Sommer, J.; Schierle, S.; Willems, S.; Kaiser, A.; Schmidt, J.; Merk, D. A new FXR ligand chemotype with agonist/antagonist switch. ACS Med. Chem. Lett., 2021, 12, 267–274.
(72) Brunst, S.; Kramer, J.; Kilu, W.; Heering, J.; Pollinger, J.; Hiesinger, K.; George, S.; Steinhilber, D.; Merk, D.; Proschak, E. Systematic assessment of fragment identification for multi‐target drug design. ChemMedChem, 2021, 16, 1088–1092.
(71) Chaikuad, A.; Pollinger, J.; Rühl, M.; Ni, X.; Kilu, W.; Heering, J.; Merk, D. Comprehensive set of tertiary complex structures and palmitic acid binding provide molecular insights into ligand design for RXR isoforms. Int. J. Mol. Sci., 2020, 21, 8457.
(70) Meijer, I.; Willems, S.; Ni, X.; Heering, J.; Chaikuad, A.; Merk, D. Chemical starting matter for HNF4α ligand discovery and chemogenomics. Int. J. Mol. Sci., 2020, 21, 7895.
(69) Heitel, P.; Faudone, G.; Helmstädter, M.; Schmidt, J.; Kaiser, A.; Tjaden, A.; Schröder, M.; Müller-Knapp, S.; Schierle, S.; Pollinger, J.; Merk, D. A Triple Farnesoid X Receptor and Peroxisome Proliferator-Activated Receptor α/δ Activator Reverses Hepatic Fibrosis in Diet-Induced NASH in Mice. Commun. Chem., 2020, 3, 174.
(68) Hinnah, K.; Willems, S.; Morstein, J.; Heering, J.; Hartrampf, F.; Broichhagen, J.; Leippe, P.; Merk, D.; Trauner, D. Photohormones Enable Optical Control of the Peroxisome Proliferator-Activated Receptor Gamma (PPARg). J. Med. Chem., 2020, 63, 10908–10920.
(67) Schierle, S.; Neumann, S.; Heitel, P.; Willems, S.; Kaiser, A.; Pollinger, J.; Merk, D. Design and structural optimization of dual FXR/PPARδ activators. J. Med. Chem., 2020, 63, 8369–8379.
(66) Willems, S.; Kilu, W.; Ni, X.; Chaikuad, A.; Knapp, S.; Heering, J.; Merk, D. The orphan nuclear receptor Nurr1 is responsive to non-steroidal anti-inflammatory drugs. Commun. Chem., 2020, 3, 85.
(65) Gellrich, L.; Heitel, P.; Heering, J.; Kilu, W.; Pollinger, J.; Goebel, T.; Kahnt, A.; Arifi, S.; Pogoda, W.; Paulke, A.; Steinhilber, D.; Proschak, E.; Wurglics, M.; Schubert-Zsilavecz, M.; Chaikuad, A.; Knapp, S.; Bischoff, I.; Fürst, R.; Merk, D. L-thyroxin and the non-classical thyroid hormone TETRAC are potent activators of PPARγ. J. Med. Chem., 2020, 63, 6727–6740.
(64) Hanke, T.; Cheung, S.-Y.; Kilu, W.; Heering, J.; Ni, X.; Planz, V.; Schierle, S.; Faudone, G.; Friedrich, M; Wanior, M.; Werz, O.; Windbergs, M.; Proschak, E.; Schubert-Zsilavecz, M.; Chaikuad, A.; Knapp, S.; Merk, D. A selective modulator of peroxisome proliferator-activated receptor γ with unprecedented binding mode. J. Med. Chem., 2020, 63, 4555–4561.
(63) Moret, M.; Friedrich, L.; Grisoni, F.; Merk, D.; Schneider, G. Generative molecular design in low data regimes. Nat. Mach. Intell., 2020, 2, 171–180.
(62) Morstein, J.; Trads, J.; Hinnah, K.; Willems, S.; Barber, D.; Trauner, M.; Merk, D.; Trauner, D. Optical Control of the Nuclear Bile Acid Receptor FXR with a Photohormone. Chem. Sci., 2020, 11, 429–434.
(61) Schierle, S.; Helmstädter, M.; Schmidt, J.; Hartmann, M.; Horz, M.; Kaiser, A.; Weizel, L.; Heitel, P.; Proschak, A.; Hernandez-Olmos, V.; Proschak, E.; Merk, D. Dual farnesoid X receptor/soluble epoxide hydrolase modulators derived from Zafirlukast. ChemMedChem, 2020, 15, 50–67.
(60) Bruns, D.; Merk, D.; Kumar, K.; Baumgartner, M.; Schneider, G. Synthetic activators of cell migration designed by constructive machine learning. Chemistry Open, 2019, 8, 1303–1308.
(59) Pollinger, J.; Schierle, S.; Gellrich, L.; Ohrndorf, J.; Kaiser, A.; Heitel, P.; Chaikuad, A.; Knapp, S.; Merk, D. A novel biphenyl-based chemotype of retinoid X receptor ligands enables subtype- and heterodimer-preference. ACS Med. Chem. Letters, 2019, 10(9), 1346–1352.
(58) Kramer, J.; Woltersdorf, S.; Duflot, T.; Hiesinger, K.; Lillich, F.; Knöll, F.; Wittmann, S.; Klingler, F.; Brunst, S.; Chaikuad, A.; Morisseau, C.; Hammock, B.; Buccellati, C.; Sala, A.; Rovati, E.; Leuillier, M.; Fraineau, S.; Rondeaux, J.; Hernandez Olmos, V.; Heering, J.; Merk, D.; Pogoryelov, D.; Steinhilber, D.; Knapp, S.; Bellien, J.; Proschak, E. Discovery of first in vivo active inhibitors of soluble epoxide hydrolase (sEH) phosphatase domain. J. Med. Chem., 2019, 62(18), 8443–8460.
(57) Hernandez-Olmos, V.; Knape, T.; Heering, J.; von Knethen, A.; Kilu, W.; Kaiser, A.; Wurglics, M.; Helmstädter, M.; Merk, D.; Schubert-Zsilavecz, M.; Parnham, M.; Steinhilber, D.; Proschak, E. Structure Optimization of a New Class of PPARγ Antagonists. Bioorg. Med. Chem., 2019, 27(21), 115082.
(56) Schierle, S.; Merk, D. Therapeutic modulation of retinoid X receptors – SAR and therapeutic potential of RXR ligands and recent patents. Expert Opin. Ther. Pat., 2019, 29(8), 605–621.
(55) Merk, D.; Sreeramulu, S.; Kudlinzki, D.; Saxena, K.; Linhard, V.; Gande, S.; Hiller, F.; Lamers, C.; Nilsson, E.; Aagaard, A.; Wissler, L.; Dekker, N.; Bamberg, K.; Schubert Zsilavecz, M.; Schwalbe, H. Molecular tuning of farnesoid X receptor partial agonism. Nat. Commun., 2019, 10, 2915.
(54) Pollinger, J.; Schierle, S.; Neumann, S.; Ohrndorf, J.; Kaiser, A.; Merk, D. Computer-assisted selective optimization of side-activities - from cinalukast to a PPARα modulator. ChemMedChem, 2019, 14, 1343–1348.
(53) Hye Khan, M. A.; Schmidt, J.; Stavniichuk, A.; Imig, J.; Merk, D. A dual farnesoid X receptor/soluble epoxide hydrolase modulator treats non-alcoholic steatohepatitis in mice. Biochem. Pharmacol., 2019, 166, 212–221.
(52) Button, A.; Merk, D.; Hiss, J.; Schneider, G. Automated de novo molecular design by hybrid machine intelligence and rule-driven chemical synthesis. Nat. Mach. Intell., 2019, 1, 307–315.
(51) Grisoni, F.; Merk, D.; Friedrich, L.; Schneider, G. Design of natural-product-inspired multi-target ligands by machine learning. ChemMedChem, 2019, 14, 1129–1134.
(50) Goebel, T.; Diehl, O.; Wittmann, S.; Merk, D.; Angioni, C.; Buscató, E.; Kottke, R.; Heering, J.; Weizel, L.; Schader, T.; Maier, T.; Geisslinger, G.; Schubert-Zsilavecz, M.; Steinhilber, D.; Proschak, E.; Kahnt, A. Zafirlukast is a dual modulator of human soluble epoxide hydrolase and PPARgamma. Front. Pharmacol., 2019, 10, 263.
(49) Pollinger, J.; Gellrich, L.; Schierle, S.; Kilu, W.; Schmidt, J.; Kalinowsky, L.; Ohrndorf, J.; Kaiser, A.; Heering, J.; Proschak, E.; Merk, D. Tuning nuclear receptor selectivity of Wy14,643 towards selective retinoid X receptor modulation. J. Med. Chem., 2019, 62(4), 2112–2126.
(48) Heering, J.; Merk, D. Hybrid Reporter Gene Assays: Versatile In Vitro Tools to Characterize Nuclear Receptor Modulators. Methods Mol. Biol. 2019, 1966, 175–192.
(47) Heitel, P.; Gellrich, L.; Kalinowsky, L.; Heering, J.; Kaiser, A.; Ohrndorf, J.; Proschak, E.; Merk, D. Computer-Assisted Discovery and Structural Optimization of a Novel Retinoid X Receptor Agonist Chemotype. ACS Med. Chem. Letters, 2019, 10(2), 203–208.
(46) Heidenreich, D.; Moustakim, M; Schmidt, J.; Merk, D.; Brennan, P.; Fedorov, O.; Chaikuad, A.; Knapp, S. A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL). J. Med. Chem., 2018, 61(23), 10929–10934.
(45) Grisoni, F.; Merk, D.; Byrne, R.; Schneider, G. Scaffold-Hopping from Synthetic Drugs by Holistic Molecular Representation. Sci. Rep., 2018, 8, 16469.
(44) Schierle, S.; Schmidt, J.; Kaiser, A.; Merk, D. Selective optimization of Pranlukast to farnesoid X receptor modulators. ChemMedChem, 2018, 13(23), 2530–2545.
(43) Merk, D.; Grisoni, F.; Friedrich, L.; Schneider, G. Tuning artificial intelligence on the de novo design of natural-product-inspired retinoid X receptor modulators. Commun. Chem., 2018, 1, 68.
(42) Heitel, P.; Gellrich, L.; Heering, J.; Goebel, T.; Kahnt, S.; Proschak, E.; Schubert-Zsilavecz, M.; Merk, D. Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro. Sci. Rep., 2018, 8, 14658.
(41) Merk, D.; Grisoni, F.; Schaller, K.; Friedrich, L.; Schneider, G. Discovery of novel molecular frameworks of farnesoid X receptor modulators by ensemble machine learning. Chemistry Open, 2018, 8(1), 7–14.
(40) Proschak, E.; Stark, H.; Merk, D. Polypharmacology by Design: A Medicinal Chemist's Perspective on Multitargeting Compounds. J. Med. Chem., 2019, 62(2), 420–444.
(39) Grisoni, F.; Merk, D.; Consonni, V.; Hiss, J.; Tagliabue, S.; Todeschini, R.; Schneider, G. Scaffold hopping from natural products to synthetic mimetics by holistic molecular similarity. Commun. Chem., 2018, 1, 44.
(38) Schmidt, J.; Schierle, S.; Gellrich, L.; Kaiser, A.; Merk, D. Structural optimization and in vitro profiling of N-phenylbenzamide-based farnesoid X receptor antagonists. Bioorg. Med. Chem., 2018, 26(14), 4240–4253.
(37) Schierle, S.; Flauaus, C.; Heitel, P.; Willems, S.; Schmidt, J.; Kaiser, A.; Weizel, L.; Goebel, T.; Kahnt, S.; Geisslinger, G.; Steinhilber, D.; Wurglics, M.; Rovati, E.; Schmidtko, A.; Proschak, E.; Merk, D. Boosting anti-inflammatory potency of zafirlukast by designed polypharmacology. J. Med. Chem., 2018, 61(13), 5758–5764.
(36) Merk, D.; Grisoni, F.; Friedrich, L.; Gelzinyte, E.; Schneider, G. Computer-assisted discovery of retinoid X receptor modulating natural products and isofunctional mimetics. J. Med. Chem., 2018, 61(12), 5442–5447.
(35) Gabler, M.; Kramer, S.; Schmidt, J.; Pollinger, J.; Weber, J.; Kaiser, A.; Löhr, F.; Proschak, E.; Schubert-Zsilavecz, M.; Merk, D. Allosteric modulation of the farnesoid X receptor by a small molecule. Sci. Rep., 2018, 8, 6846.
(34) Merk, D.; Grisoni, F.; Friedrich, L.; Gelzinyte, E.; Schneider, G. Scaffold hopping from synthetic RXR modulators by virtual screening and de novo design. Med. Chem. Commun., 2018, 9, 1289–1292.
(33) Schierle, S.; Merk, D. Development of nuclear receptor modulators. Methods Mol. Biol. 2018, 1824, 245-260.
(32) Merk, D.; Friedrich, L.; Grisoni, F.; Schneider, G. De novo design of bioactive small molecules by artificial intelligence. Mol. Inform. 2018, 37, 1700153.
(31) Gellrich, L.; Merk, D. Therapeutic potential of peroxisome proliferator-activated receptor modulation in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Nuclear Receptor Research 2017, 4, 101310.
(30) Schmidt, J.; Rotter, M.; Weiser, T.; Wittmann, S.; Weizel, L.; Kaiser, A.; Heering, J.; Goebel, T.; Angioni, C.; Wurglics, M.; Paulke, A.; Geisslinger, G.; Kahnt, A.; Steinhilber, D.; Proschak, E.; Merk, D. A dual modulator of farnesoid X receptor and soluble epoxide hydrolase to counter non-alcoholic steatohepatitis. J. Med. Chem. 2017, 60(18), 7703–7724.
(29) Flesch, D.; Cheung, S.; Schmidt, J.; Gabler, M.; Heitel, P.; Kramer, J.; Kaiser, A.; Hartmann, M.; Lindner, M.; Lüddens-Dämgen, K.; Heering, J.; Lamers, C.; Lüddens, H.; Wurglics, M.; Proschak, E.; Schubert-Zsilavecz, M.; Merk, D. Non-acidic farnesoid X receptor agonists. J. Med. Chem. 2017, 60(16), 7199–7205.
(28) Proschak, E.; Heitel, P.; Kalinowsky, L.; Merk, D. Opportunities and challenges for fatty acid mimetics in drug discovery. J. Med. Chem., 2017, 60(13), 5235–5266.
(27) Heitel, P.; Achenbach, J.; Moser, D.; Proschak, E.; Merk, D. DrugBank screening revealed alitretinoin and bexarotene as liver X receptor modulators. Bioorg. Med. Chem. Lett., 2017, 27(5), 1193–1198.
(26) Pollinger, J.; Merk, D. Therapeutic applications of the versatile fatty acid mimetic WY14643. Expert Opin. Ther. Pat., 2016, 27(4), 517–525.
(25) Blöcher, R.; Lamers, C.; Wittmann, S.; Diehl, O.; Hanke, T.; Merk, D.; Steinhilber, D.; Schubert-Zsilavecz, M.; Kahnt, A.; Proschak E. Design and synthesis of fused soluble epoxide hydrolase/ peroxisome proliferator-activated receptor modulators. Med. Chem. Commun., 2016, 7: 1209–1216.
(24) Lamers, C.; Merk, D.; Gabler, M.; Flesch, D.; Schubert-Zsilavecz, M. SAR-studies on FXR modulators with an aryloxypropyloxybenzoic acid scaffold led to the discovery of the first combined FXR antagonistic/TGR5 agonistic compound. Future Med. Chem., 2015, 8(2): 133–148.
(23) Hanke, T. & Merk, D.; Steinhilber, D.; Geisslinger, G.; Schubert-Zsilavecz, M. Small molecules with anti-inflammatory properties in clinical development. Pharmacol. Ther., 2016, 157, 163–187.
(22) Blöcher, R.; Lamers, C.; Wittmann, S.; Merk, D.; Hartmann, M.; Weizel, L.; Diehl, O.; Brüggerhof, A.; Boß, M.; Kaiser, A.; Schader, T.; Göbel, T.; Grundmann, M.; Angioni, C.; Geisslinger, G.; Wurglics, M.; Kostenis, E.; Brüne, B.; Steinhilber, D.; Schubert-Zsilavecz, M.; Kahnt, A.; Proschak E. N-Benzylbenzamides: a novel merged scaffold for orally available dual sEH/PPARγ modulators. J. Med. Chem., 2016, 59(1): 61–81.
(21) Merk, D. Chances and challenges of retinoid X receptor gamma targeting for regenerative multiple sclerosis treatment. Future Med. Chem., 2015, 7(18), 2411–2413.
(20) Schmidt, J.; Klingler, F.; Proschak, E.; Steinhilber, D.; Schubert-Zsilavecz, M.; Merk, D. NSAIDs ibuprofen, indometacin and diclofenac do not interact with farnesoid X receptor. Sci. Rep., 2015, 5, 14782.
(19) Merk, D.; Zettl, M.; Steinhilber, D.; Werz, O.; Schubert-Zsilavecz, M. Pirinixic acids: flexible fatty acid mimetics with various biological activities. Future Med. Chem., 2015, 12(7), 1597–1616.
(18) Merk, D.; Schubert-Zsilavecz, M. Natural compound renews hope for diabetes and obesity therapeutic target. Future Med. Chem., 2015, 7(7), 833–35.
(17) Flesch, D.; Gabler, M.; Lill, A.; Gomez, R.; Steri, R.; Schneider, G.; Stark, H.; Schubert-Zsilavecz, M.; Merk, D. Fragmentation of GW4064 led to a highly potent partial farnesoid X receptor agonist with improved drug-like properties. Bioorg. Med. Chem., 2015, 23(13), 3490–3498.
(16) Merk, D. & Lamers, C.; Weber, J.; Flesch, D.; Gabler M.; Proschak, E.; Schubert-Zsilavecz, M. Anthranilic acid derivatives as nuclear receptor modulators – development of novel PPAR selective and dual PPAR/FXR ligands. Bioorg. Med. Chem., 2015, 23(3), 499–514.
(15) Pellowska, M.; Stein, C.; Pohland, M.; Merk, D.; Klein, J., Eckert, G.P.; Schubert-Zsilavecz, M.; Wurglics, M. Pharmakokinetic properties of MH84, a γ-secretase modulator with PPARγ agonistic activity. J. Pharm. Biomed. Analysis, 2015, 102, 417–424.
(14) Lamers, C.; Schubert-Zsilavecz, M.; Merk, D. Medicinal Chemistry and Pharmacological Potential of FXR antagonists. Curr. Trends Med. Chem., 2014, 14(19), 2188–2205.
(13) Merk, D.; Lamers, C.; Ahmad, K.; Carrasco Gomez, R.; Schneider, G.; Steinhilber, D.; Schubert-Zsilavecz, M. Extending the structure-activity relationship of anthranilic acid derivatives as farnesoid X receptor modulators – Development of a highly potent partial farnesoid X receptor agonist. J. Med. Chem., 2014, 57(19), 8035–8055.
(12) Merk, D.; Gabler, M.; Gomez, R..; Flesch, D.; Hanke, T.; Kaiser, A.; Lamers, C.; Werz, O.; Schneider, G.; Schubert-Zsilavecz, M. Anthranilic acid derivatives as novel ligands for farnesoid X receptor (FXR). Bioorg. Med. Chem., 2014, 22(8), 2447–2460.
(11) Merk, D.; Steinhilber, D.; Schubert-Zsilavecz, M. Characterizing ligands for farnesoid X receptor - available in vitro test systems for farnesoid X receptor modulator development. Expert Opin. Drug Discov., 2014, 9(1), 27–37.
(10) Merk, D.; Schubert-Zsilavecz, M. Repairing mutated proteins – development of small molecules targeting defects in the cystic fibrosis transmembrane conductance regulator. Expert Opin. Drug. Discov., 2013, 8(6), 691–708.
(9) Pellowska, M.; Merk, D.; Schubert-Zsilavecz M. Advances in personalized medicine – medicinal chemistry and pharmacology of vemurafenib and ivacaftor. Pharmazie, 2013, 68(7), 484–491.
(8) Flesch, D.; Merk, D.; Lamers, C.; Schubert-Zsilavecz, M. Novel prostaglandin receptor modulators: a patent review (2002 - 2012) – part II: EP receptor modulators. Expert Opin. Ther. Pat., 2013, 23(2), 233–267.
(7) Lamers, C.; Flesch, D.; Schubert-Zsilavecz, M.; Merk, D. Novel prostaglandin receptor modulators: a patent review (2002 - 2012) – part I: non-EP receptor modulators. Expert Opin. Ther. Pat., 2013, 23(1), 47–77.
(6) Merk, D.; Schubert-Zsilavecz, M. Novel strategies to control lipid metabolism: can the antisense drug mipomersen fulfill the unmet need? Future Med. Chem., 2012, 4(14), 1773–1775.
(5) Lamers, C.; Schubert-Zsilavecz, M.; Merk, D. Therapeutic modulators of peroxisome proliferator-activated receptors (PPAR): a patent review (2008–present). Expert Opin. Ther. Pat., 2012, 22(7), 803–841.
(4) Merk, D.; Steinhilber, D.; Schubert-Zsilavecz, M. Medicinal chemistry of farnesoid X receptor ligands: from agonists and antagonists to modulators. Future Med. Chem., 2012, 4(8), 1015–1036.
(3) Merk, D.; Schubert-Zsilavecz, M. Nuclear receptors as pharmaceutical targets: rise of FXR and rebirth of PPAR? Future Med. Chem., 2012, 4(5), 587–588.
(2) Merk, D.; Schubert-Zsilavecz, M. New hope or drawbacks: will chronic kidney disease be treatable with small molecules in the near future? Future Med. Chem., 2012, 4(3), 269–271.
(1) Schubert-Zsilavecz, M.; Merk, D. Innovations in the treatment of cystic fibrosis: outriders for the treatment of diseases with other genetic defects? Future Med. Chem., 2011, 3(16), 1969–1970.
(3) John Imig, Daniel Merk, Md Abdul Hye Khan: US62/902,771 Compounds and compositions for treating kidney disease (2019, filed).
(2) Daniel Merk, Pascal Heitel, Jurema Schmidt, Manfred Schubert-Zsilavecz: WO2019057969A1 Dual agonists of FXR and PPARδ and their uses (2019, granted).
(1) Daniel Merk, Jurema Schmidt, Manfred Schubert-Zsilavecz, Ewgenij Proschak: WO2018215610A1 Dual modulators of farnesoid X receptor and soluble epoxide hydrolase (2018, granted).
(4) Lamers, C.; Merk, D. Discovery, structural refinement and therapeutic potential of farnesoid X receptor activators in Anti-fibrotic Drug Discovery. Editors: Jehrod Brenneman, Malliga R Iyer. London, UK: Royal Society of Chemistry. ISBN: 978-1788015103.
(3) Merk, D.; Schubert-Zsilavecz, M. (2018). The linker approach: drug conjugates in Drug Selectivity - an evolving concept in medicinal chemistry. Editors: Norbert Handler, Helmut Buschmann. Weinheim, DE: Wiley-VCH Verlag GmbH & Co. KGaA. ISBN: 978-3-527-33538-1
(2) Wurglics, M.; Lamers, C.; Merk, D. (2016). Arbeitsbuch Stöchiometrie. Eschborn. DE: Govi Verlag. ISBN: 978-3-7741-1310-7
(1) Ammon, Hermann P. T.; Schubert-Zsilavecz, Manfred (2014). Hunnius Pharmazeutisches Wörterbuch (11th Edition). Berlin, DE: De Gruyter. ISBN: 978-3-11-030990-4 Contribution to chapters of organic chemistry and inorganic chemistry.