Main Content

Publications

Original articles

  • Wannowius, M., Neelen, C., Lotz, P., Daude, M., Neubauer, A., Fühler, B., Diederich, W. E., & Geyer, J. (2024). Structure-Activity Relationships and Target Selectivity of Phenylsulfonylamino-Benzanilide Inhibitors Based on S1647 at the SLC10 Carriers ASBT, NTCP, and SOAT. J Med Chem. 2024 Oct 17.
    https://doi.org/10.1021/acs.jmedchem.4c01743

    Epub ahead of print

  • Kurz, M., Ulrich, M., Kirchhofer, S. B., Bittner, A., Daude, M., Diederich, W. E., Pauck, K., Garn, H., & Bünemann, M. (2024). Arachidonic Acid Directly Activates the Human DP2 Receptor. Mol Pharmacol. 2024 Oct 17;106(5):216-224.
    https://doi.org/10.1124/molpharm.124.000884

  • Brichkina, A., Ems, M., Suezov, R., Singh, R., Lutz, V., Picard, F. S. R., Nist, A., Stiewe, T., Graumann, J., Daude, M., Diederich, W. E., Finkernagel, F., Chung, H. R., Bartsch, D. K., Roth, K., Keber, C., Denkert, C., Huber, M., Gress, T. M., & Lauth, M. (2024). DYRK1B blockade promotes tumoricidal macrophage activity in pancreatic cancer. Gut, 73(10), 1684–1701.
    https://doi.org/10.1136/gutjnl-2023-331854

  • Hochban, P. M. M., Heyder, L., Heine, A., & Diederich, W. E. (2024). What doesn't fit is made to fit: Pim-1 kinase adapts to the configuration of stilbene-based inhibitors. Arch Pharm (Weinheim). 2024 Jun;357(6):e2400094.
    https://doi.org/10.1002/ardp.202400094

  • Koeniger, A., Polo, P., Brichkina, A., Finkernagel, F., Visekruna, A., Nist, A., Stiewe, T., Daude, M., Diederich, W. E., Gress, T. M., Adhikary, T., & Lauth, M. (2023). Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment. NAR cancer, 5(1), zcad007.
    https://doi.org/10.1093/narcan/zcad007

  • Heyder, L., Hochban, P. M. M., Taylor, C., Chevillard, F., Siefker, C., Iking, C., Borchardt, H., Aigner, A., Klebe, G., Heine, A., Kolb, P., & Diederich, W. E. (2023). Pose, duplicate, then elaborate: Steps towards increased affinity for inhibitors targeting the specificity surface of the Pim-1 kinase. Eur J Med Chem, 245(Pt 1), 114914.
    https://doi.org/10.1016/j.ejmech.2022.114914

  • Reher, R., Aron, A. T., Fajtová, P., Stincone, P., Wagner, B., Pérez-Lorente, A. I., Liu, C., Shalom, I. Y. B., Bittremieux, W., Wang, M., Jeong, K., Matos-Hernandez, M. L., Alexander, K. L., Caro-Diaz, E. J., Naman, C. B., Scanlan, J. H. W., Hochban, P. M. M., Diederich, W. E., Molina-Santiago, C., Romero, D., ... Petras, D. (2022). Native metabolomics identifies the rivulariapeptolide family of protease inhibitors. Nat Commun, 13(1), 4619.
    https://doi.org/10.1038/s41467-022-32016-6

  • Sandner, A., Ngo, K., Sager, C. P., Scheer, F., Daude, M., Diederich, W. E., Heine, A., & Klebe, G. (2021). Which Properties Allow Ligands to Open and Bind to the Transient Binding Pocket of Human Aldose Reductase? Biomolecules, 11(12), 1837.
    https://doi.org/10.3390/biom11121837

  • Schencking, I., Schäfer, E. M., Scanlan, J. H. W., Wenzel, B. M., Emmerich, R. E., Steinmetzer, T., Diederich, W. E., Schlitzer, M., & Hartmann, R. K. (2021). RNase P Inhibitors Identified as Aggregators. Antimicrob Agents Chemother, 65(8), e0030021.
    https://doi.org/10.1128/AAC.00300-21

  • Koeniger, A., Brichkina, A., Nee, I., Dempwolff, L., Hupfer, A., Galperin, I., Finkernagel, F., Nist, A., Stiewe, T., Adhikary, T., Diederich, W., & Lauth, M. (2021). Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy. Cancers, 13(8), 1908.
    https://doi.org/10.3390/cancers13081908

  • Venegas, F. A., Köllisch, G., Mark, K., Diederich, W. E., Kaufmann, A., Bauer, S., Chavarría, M., Araya, J. J., & García-Piñeres, A. J. (2019). The Bacterial Product Violacein Exerts an Immunostimulatory Effect Via TLR8. Sci Rep, 9(1), 13661.
    https://doi.org/10.1038/s41598-019-50038-x

  • Legrand, N., Bretscher, C. L., Zielke, S., Wilke, B., Daude, M., Fritz, B., Diederich, W. E., & Adhikary, T. (2019). PPARβ/δ recruits NCOR and regulates transcription reinitiation of ANGPTL4. Nucleic Acids Res, 47(18), 9573-9591.
    https://doi.org/10.1093/nar/gkz685

  • Kanitz, M., Blanck, S., Heine, A., Gulyaeva, A. A., Gorbalenya, A. E., Ziebuhr, J., & Diederich, W. E. (2019). Structural basis for catalysis and substrate specificity of a 3C-like cysteine protease from a mosquito mesonivirus. Virology, 533, 21-33.
    https://doi.org/10.1016/j.virol.2019.05.001

  • Jelinek, A., Heyder, L., Daude, M., Plessner, M., Krippner, S., Grosse, R., Diederich, W. E., & Culmsee, C. (2018). Mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis. Free Radic Biol Med, 117, 45-57.
    https://doi.org/10.1016/j.freeradbiomed.2018.01.019

  • Chevillard, F., Rimmer, H., Betti, C., Pardon, E., Ballet, S., van Hilten, N., Steyaert, J., Diederich, W. E., & Kolb, P. (2018). Binding-Site Compatible Fragment Growing Applied to the Design of β2-Adrenergic Receptor Ligands. J Med Chem, 61(3), 1118-1129.
    https://doi.org/10.1021/acs.jmedchem.7b01558

  • Ehlert, F. G. R., Linde, K., & Diederich, W. E. (2017). What Are We Missing? The Detergent Triton X-100 Added to Avoid Compound Aggregation Can Affect Assay Results in an Unpredictable Manner. ChemMedChem, 12(17), 1419-1423.
    https://doi.org/10.1002/cmdc.201700329

  • Niu, X., Brahmbhatt, H., Mergenthaler, P., Zhang, Z., Sang, J., Daude, M., Ehlert, F. G. R., Diederich, W. E., Wong, E., Zhu, W., Pogmore, J., Nandy, J. P., Satyanarayana, M., Jimmidi, R. K., Arya, P., Leber, B., Lin, J., Culmsee, C., Yi, J., & Andrews, D. W. (2017). A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection. Cell Chem Biol, 24(4), 493-506.e5.
    https://doi.org/10.1016/j.chembiol.2017.03.011

  • Rechlin, C., Scheer, F., Terwesten, F., Wulsdorf, T., Pol, E., Fridh, V., Toth, P., Diederich, W. E., Heine, A., & Klebe, G. (2017). Price for Opening the Transient Specificity Pocket in Human Aldose Reductase upon Ligand Binding: Structural, Thermodynamic, Kinetic, and Computational Analysis. ACS Chem Biol, 12(5), 1397-1415.
    https://doi.org/10.1021/acschembio.7b00062

  • Coburger, I., Schaub, Y., Roeser, D., Hardes, K., Maeder, P., Klee, N., Steinmetzer, T., Imhof, D., Diederich, W. E., & Than, M. E. (2016). Identification of inhibitors of the transmembrane protease FlaK of Methanococcus maripaludis. MicrobiologyOpen, 5(4), 637-646.
    https://doi.org/10.1002/mbo3.358

  • Toth, P. M., Lieber, S., Scheer, F. M., Schumann, T., Schober, Y., Nockher, W. A., Adhikary, T., Müller-Brüsselbach, S., Müller, R., & Diederich, W. E. (2016). Design and Synthesis of Highly Active Peroxisome Proliferator-Activated Receptor (PPAR) β/δ Inverse Agonists with Prolonged Cellular Activity. ChemMedChem, 11(5), 488-496.
    https://doi.org/10.1002/cmdc.201500594

  • Schiebel, J., Radeva, N., Köster, H., Metz, A., Krotzky, T., Kuhnert, M., Diederich, W. E., Heine, A., Neumann, L., Atmanene, C., Roecklin, D., Vivat-Hannah, V., Renaud, J. P., Meinecke, R., Schlinck, N., Sitte, A., Popp, F., Zeeb, M., & Klebe, G. (2015). One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists. ChemMedChem, 10(9), 1511-1521.
    https://doi.org/10.1002/cmdc.201500267

  • Kuhnert, M., Blum, A., Steuber, H., & Diederich, W. E. (2015). Privileged Structures Meet Human T-Cell Leukemia Virus-1 (HTLV-1): C2-Symmetric 3,4-Disubstituted Pyrrolidines as Nonpeptidic HTLV-1 Protease Inhibitors. J Med Chem, 58(11), 4845-4850.
    https://doi.org/10.1021/acs.jmedchem.5b00346

  • Schumann, T., Adhikary, T., Wortmann, A., Finkernagel, F., Lieber, S., Schnitzer, E., Legrand, N., Schober, Y., Nockher, W. A., Toth, P. M., Diederich, W. E., Nist, A., Stiewe, T., Wagner, U., Reinartz, S., Müller-Brüsselbach, S., & Müller, R. (2015). Deregulation of PPARβ/δ target genes in tumor-associated macrophages by fatty acid ligands in the ovarian cancer microenvironment. Oncotarget, 6(15), 13416-13433.
    https://doi.org/10.18632/oncotarget.3826

  • Adhikary, T., Wortmann, A., Schumann, T., Finkernagel, F., Lieber, S., Roth, K., Toth, P. M., Diederich, W. E., Nist, A., Stiewe, T., Kleinesudeik, L., Reinartz, S., Müller-Brüsselbach, S., & Müller, R. (2015). The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state. Nucleic Acids Res, 43(10), 5033-5051.
    https://doi.org/10.1093/nar/gkv331

  • Kuhnert, M., Köster, H., Bartholomäus, R., Park, A. Y., Shahim, A., Heine, A., Steuber, H., Klebe, G., & Diederich, W. E. (2015). Tracing binding modes in hit-to-lead optimization: chameleon-like poses of aspartic protease inhibitors. Angew Chem Int Ed Engl., 54(9), 2849-2853.
    https://doi.org/10.1002/anie.201411206

  • de Sousa, L. R., Wu, H., Nebo, L., Fernandes, J. B., da Silva, M. F., Kiefer, W., Kanitz, M., Bodem, J., Diederich, W. E., Schirmeister, T., & Vieira, P. C. (2015). Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies. Bioorg Med Chem, 23(3), 466-470.
    https://doi.org/10.1016/j.bmc.2014.12.015

  • Wu, H., Bock, S., Snitko, M., Berger, T., Weidner, T., Holloway, S., Kanitz, M., Diederich, W. E., Steuber, H., Walter, C., Hofmann, D., Weißbrich, B., Spannaus, R., Acosta, E. G., Bartenschlager, R., Engels, B., Schirmeister, T., & Bodem, J. (2015). Novel dengue virus NS2B/NS3 protease inhibitors. Antimicrob Agents Chemother, 59(2), 1100-1109.
    https://doi.org/10.1128/AAC.03543-14

  • Lieber, S., Scheer, F., Finkernagel, F., Meissner, W., Giehl, G., Brendel, C., Diederich, W. E., Müller-Brüsselbach, S., & Müller, R. (2015). The inverse agonist DG172 triggers a PPARβ/δ-independent myeloid lineage shift and promotes GM-CSF/IL-4-induced dendritic cell differentiation. Mol Pharmacol, 87(2), 162-173.
    https://doi.org/10.1124/mol.114.094672

  • Kuhnert, M., Steuber, H., & Diederich, W. E. (2014). Structural basis for HTLV-1 protease inhibition by the HIV-1 protease inhibitor indinavir. J Med Chem, 57(14), 6266-6272.
    https://doi.org/10.1021/jm500402c

  • Adhikary, T., Brandt, D. T., Kaddatz, K., Stockert, J., Naruhn, S., Meissner, W., Finkernagel, F., Obert, J., Lieber, S., Scharfe, M., Jarek, M., Toth, P. M., Scheer, F., Diederich, W. E., Reinartz, S., Grosse, R., Müller-Brüsselbach, S., & Müller, R. (2013). Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion. Oncogene, 32(44), 5241-5252.
    https://doi.org/10.1038/onc.2012.549

  • Lieber, S., Scheer, F., Meissner, W., Naruhn, S., Adhikary, T., Müller-Brüsselbach, S., Diederich, W. E., & Müller, R. (2012). (Z)-2-(2-bromophenyl)-3-{[4-(1-methyl-piperazine)amino]phenyl}acrylonitrile (DG172): an orally bioavailable PPARβ/δ-selective ligand with inverse agonistic properties. J Med Chem, 55(6), 2858-2868.
    https://doi.org/10.1021/jm2017122

  • Toth, P. M., Naruhn, S., Pape, V. F., Dörr, S. M., Klebe, G., Müller, R., & Diederich, W. E. (2012). Development of improved PPARβ/δ inhibitors. ChemMedChem, 7(1), 159-170.
    https://doi.org/10.1002/cmdc.201100408.

  • Naruhn, S., Toth, P. M., Adhikary, T., Kaddatz, K., Pape, V., Dörr, S., Klebe, G., Müller-Brüsselbach, S., Diederich, W. E., & Müller, R. (2011). High-affinity peroxisome proliferator-activated receptor β/δ-specific ligands with pure antagonistic or inverse agonistic properties. Mol Pharmacol, 80(5), 828-838.
    https://doi.org/10.1124/mol.111.074039

  • Blum, A., Böttcher, J., Dörr, S., Heine, A., Klebe, G., & Diederich, W. E. (2011). Two solutions for the same problem: multiple binding modes of pyrrolidine-based HIV-1 protease inhibitors. J Mol Biol, 410(4), 745-755.
    https://doi.org/10.1016/j.jmb.2011.04.052

  • Selbach, S., Diederich, W. E., Fett, S., Fründ, D., Koch, T., & Eberhart, L. H. (2011). Stability-indicating HPLC assays for the determination of piritramide and droperidol in PCA solution. J Clin Pharm Ther, 36(2), 161-165.
    https://doi.org/10.1111/j.1365-2710.2010.01169.x

  • Englert, L., Silber, K., Steuber, H., Brass, S., Over, B., Gerber, H. D., Heine, A., Diederich, W. E., & Klebe, G. (2010). Fragment-based lead discovery: screening and optimizing fragments for thermolysin inhibition. ChemMedChem, 5(6), 930-940.
    https://doi.org/10.1002/cmdc.201000084

  • Luksch, T., Blum, A., Klee, N., Diederich, W. E., Sotriffer, C. A., & Klebe, G. (2010). Pyrrolidine derivatives as plasmepsin inhibitors: binding mode analysis assisted by molecular dynamics simulations of a highly flexible protein. ChemMedChem, 5(3), 443-454.
    https://doi.org/10.1002/cmdc.200900452

  • Blum, A., Böttcher, J., Sammet, B., Luksch, T., Heine, A., Klebe, G., & Diederich, W. E. (2008). Achiral oligoamines as versatile tool for the development of aspartic protease inhibitors. Bioorg Med Chem, 16(18), 8574-8586.
    https://doi.org/10.1016/j.bmc.2008.08.012

  • Luksch, T., Chan, N. S., Brass, S., Sotriffer, C. A., Klebe, G., & Diederich, W. E. (2008). Computer-aided design and synthesis of nonpeptidic plasmepsin II and IV inhibitors. ChemMedChem, 3(9), 1323-1336.
    https://doi.org/10.1002/cmdc.200700270

  • Böttcher, J., Blum, A., Dörr, S., Heine, A., Diederich, W. E., & Klebe, G. (2008). Targeting the open-flap conformation of HIV-1 protease with pyrrolidine-based inhibitors. ChemMedChem, 3(9), 1337-1344.
    https://doi.org/10.1002/cmdc.200800113

  • Böttcher, J., Blum, A., Heine, A., Diederich, W. E., & Klebe, G. (2008). Structural and kinetic analysis of pyrrolidine-based inhibitors of the drug-resistant Ile84Val mutant of HIV-1 protease. J Mol Biol, 383(2), 347-357.
    https://doi.org/10.1016/j.jmb.2008.07.062

  • Blum, A., Böttcher, J., Heine, A., Klebe, G., & Diederich, W. E. (2008). Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold. J Med Chem, 51(7), 2078-2087.
    https://doi.org/10.1021/jm701142s

  • Gerlach, C., Münzel, M., Baum, B., Gerber, H. D., Craan, T., Diederich, W. E., & Klebe, G. (2007). KNOBLE: a knowledge-based approach for the design and synthesis of readily accessible small-molecule chemical probes to test protein binding. Angew Chem Int Ed Engl, 46(47), 9105-9109.
    https://doi.org/10.1002/anie.200703323

  • Brass, S., Chan, N. S., Gerlach, C., Luksch, T., Böttcher, J., & Diederich, W. E. (2006), Synthesis of 2,3,4,7-tetrahydro-1H-azepines as privileged ligand scaffolds for the design of aspartic protease inhibitors via a ring-closing metathesis approach. J Organomet Chem, 691, 5406-5422.
    https://doi.org/10.1016/j.jorganchem.2006.09.031

  • Brass, S., Gerber, H. D., Dörr, S., & Diederich, W. E. (2006). Facile synthesis of substituted 2,3,4,7-tetrahydro-1H-azepines via ring-closing metathesis. Tetrahedron, 62, 1777-1786.
    https://doi.org/10.1016/j.tet.2005.11.049

  • Haack, T., Haack, K., Diederich, W. E., Blackman, B., Roy, S., Pusuluri, S., & Georg, G. I. (2005). Formal total syntheses of the (-)-salicylihalamides A and B from D-glucose and L-rhamnose. J Org Chem, 70(19), 7592-7604.
    https://doi.org/10.1021/jo050750x

  • Yang, K., Blackman, B., Diederich, W., Flaherty, P. T., Mossman, C. J., Roy, S., Ahn, Y. M., & Georg, G. I. (2003). Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy. J Org Chem, 68(26), 10030-10039.
    https://doi.org/10.1021/jo0301550.

  • Yang, K., Haack, T., Blackman, B., Diederich, W. E., Roy, S., Pusuluri, S., & Georg, G. I. (2003). Enantiospecific formal total syntheses of (-)-salicylihalamides A and B from D-glucose and L-rhamnose. Org Lett, 5(21), 4007-4009.
    https://doi.org/10.1021/ol035630v

  • Diederich, W. E., & Haake, M. (2003). Synthesis and structure of novel 1λ4,2,6-thiadiazines. J Org Chem, 68(10), 3817-3830.
    https://doi.org/10.1021/jo026814a

Others

  • Galperin, I., Dempwolff, L., Diederich, W. E., & Lauth, M. (2019). Inhibiting Hedgehog: An Update on Pharmacological Compounds and Targeting Strategies. J Med Chem, 62(18), 8392-8411.
    https://doi.org/10.1021/acs.jmedchem.9b00188

  • Kuhnert, M., Diederich, W. E. (2016). Structure-Based Drug Design in Medicinal Chemistry: The Devil is in the Detail. Synlett, 27 (5), 641-649.
    https://doi.org/10.1055/s-0035-1561270

  • Wegscheid-Gerlach, C., Gerber, H. D., & Diederich, W. E. (2015). Frontiers in Medicinal Chemistry 2015: Meet the Experts of MedChem near the Cradle of Medicinal and Pharmaceutical Chemistry. ChemMedChem, 10(7), 1267-1271.
    https://doi.org/10.1002/cmdc.201500208

  • Steuber, H., Kanitz, M., Ehlert, F.G.R., Diederich, W.E. (2014). Recent Advances in Targeting Dengue and West Nile Virus Proteases Using Small Molecule Inhibitors. In: Diederich, W., Steuber, H. (eds) Therapy of Viral Infections. Topics in Medicinal Chemistry, vol 15. Springer, Berlin, Heidelberg.
    https://doi.org/10.1007/7355_2014_46

  • Kuhnert, M., Diederich, W. E.(2014). HIV-Protease-Inhibitoren. Pharmakon4, 262-269

  • Wegscheid-Gerlach, C., Gerber, H. D., & Diederich, W. E. (2010). Proteases of Plasmodium falciparum as potential drug targets and inhibitors thereof. Curr Top Med Chem, 10(3), 346-367.
    https://doi.org/10.2174/156802610790725461

  • Blum, A., Diederich, W. E. (2009) C2-symmetric pyrrolidines derived from tartaric acids: versatile chiral building blocks for total synthesis, catalyst design, supramolecular and medicinal chemistry. Curr Org Synth, 6 (1), 38-53.
    https://doi.org/10.2174/157017909787314902

  • Diederich, W., Haebel, P., Heine, A., Reuter, K., Sotriffer, C., Klebe, G. (2004) Neue Konzepte zur Arzneistoffsuche und Synthese. LaborPraxis 11, 24-26.