Publications

Publications (peer-review)

2024

(137)   Tredup, C.; Ackloo, S.; Beck, H.; Brown, P.J.; Bullock, A.N.; Ciulli, A.; Dikic, I.; Edfeldt, K.; Edwards, A.M.; Elkins, J.M.; Farin, H.F.; Fon, E.A.; Gstaiger, M.; Günther, J.; Gustavsson, A.-L.; Häberle, S.; Isigkeit, L.; Huber, K.V.M.; Kotschy, A.; Krämer, O.; Leach, A.R.; Marsden, B.D.; Matsui, H.; Merk, D.; Montel, F.; Mulder, M.P.C.; Müller, S.; Owen, D.R.; Proschak, E.; Röhm, S.; Stolz, A.; Sundström, M.; v. Delft, F.; Willson, T.M.; Arrowsmith, C.H.; Knapp, S. Toward target 2035: EUbOPEN - a public–private partnership to enable & unlock biology in the open. RSC Med. Chem., 2024, DOI: 10.1039/D4MD00735B.

(136)   Schiedel, M.; Barbie, P.; Pape, F.; Pinto, M.; Lopez, A.U.; Méndez, M.; Hessler, G.; Merk, D.; Gehringer, M.; Lamers, C. We are MedChem: The Frontiers in Medicinal Chemistry 2024. ChemMedChem, 2024, e202400543.

(135)   Reynders, M.; Willems, S.; Marschner, J. A.; Wein, T.; Merk, D.; Thorn-Seshold, O. A High-Quality Photoswitchable Probe that Selectively and Potently Regulates the Transcription Factor RORγ. Angew. Chem. Int. Ed., 2024, 63, e202410139.

(134)   Nawa, F.; Sai, M.; Vietor, J.; Schwarzenbach, R.; Bitić, A.; Wolff, S.; Ildefeld, N.; Pabel, J.; Wein, T.; Marschner, J. A.; Heering, J.; Merk, D. Tuning RXR modulators for PGC1α recruitment. J. Med. Chem., 2024, 67, 16338–16354.

(133)   Isigkeit, L.; Hörmann, T.; Schallmayer, E.; Scholz, K.; Lillich, F.F.; Ehrler, J.H.M.; Hufnagel, B.; Büchner, J.; Marschner, J.A.; Pabel, J.; Proschak, E.; Merk, D. Automated design of multi-target ligands by generative deep learning. Nat. Commun., 2024, 15, 7946.

(132)   Hank, E. C.; Sai, M.; Kasch, T.; Meijer, I.; Marschner, J. A.; Merk, D. Development of Tailless Homologue (TLX) Agonist Chemical Tools. J. Med. Chem., 2024, 67, 16598–16611.

(131)   Willems, S.; Busch, R.; Nawa, F.; Ballarotto, M.; Lillich, F.; Kasch, T.; López-García, Ú.; Marschner, J. A.; Rüger, L.; Renelt, B.; Ohrndorf, J.; Arifi, S.; Zaienne, D.; Proschak, E.; Pabel, J.; Merk, D. Structural Optimization of Oxaprozin for Selective Inverse Nurr1 Agonism. J. Med. Chem., 2024, 67, 13324–13348.

(130)   Sai, M.; Hank, E. C.; Lewandowski, M.; Kasch, T.; Marschner, J. A.; Merk, D. Development of Potent and Selective Nurr1 Agonists from Amodiaquine By Scaffold Hopping and Fragment Growing. Commun. Chem., 2024, 7, 149.

(129)   Sai, M.; van Herwijnen, N.; Merk, D. Azologs of the fatty acid mimetic drug cinalukast enable light-induced PPARα activation. ChemMedChem, 2024, e202400327.

(128)   Isigkeit, L.; Schallmayer, E.; Busch, R.; Brunello, L.; Tjaden, A.; Elson, L.; Müller, S.; Knapp, S.; Stolz, A.; Marschner, J. A.; Merk, D. Chemogenomics for NR1 nuclear hormone receptors. Nat. Commun., 2024, 15, 5201.

(127)   Atz, K.; Cotos, L.; Isert, C.; Håkansson, M.; Focht, D.; Hilleke, M.; Nippa, D.; Iff, M.; Ledergerber, J.; Schiebroek, C.; Romeo, V.; Hiss, J.; Merk, D.; Schneider, P.; Kuhn, B.; Grether, U.; Schneider, G. Prospective de novo drug design with deep interactome learning. Nat. Commun., 2024, 15, 3408.

(126)   Hernandez-Olmos, V.; Heering, J.; Marinescu, B.; Schermeng, T.; Ivanov, V.; Moroz, Y.; Nevermann, S.; Mathes, M.; Ehrler, J.; Alnouri, M. W.; Wolf, M.; Haydo, A.; Schmachtel, T.; Zaliani, A.; Höfner, G.; Kaiser, A.; Schubert-Zsilavecz, M.; Beck-Sickinger, A.; Offermanns, S.; Gribbon, P.; Rieger, M.; Merk, D.; Sisignano, M.; Steinhilber, D.; Proschak, E. Development of a Potent and Selective G2A (GPR132) Agonist. J. Med. Chem., 2024, 67, 10567–10588.

(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, 67, 2152–2164.

(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, 19, e202300379.

 

2023

(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.

 

2022

(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.

 

2021

(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.

 

2020

(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.

 

2019

(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.

 

2018

(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.

 

2017

(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.

 

2012-16

(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.

 

Patents

(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).

 

Books & Chapters

(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.