Search Results - "Möbitz, Henrik"

Discovery of Cyclic Sulfone Hydroxyethylamines as Potent and Selective β-Site APP-Cleaving Enzyme 1 (BACE1) Inhibitors: Structure-Based Design and in Vivo Reduction of Amyloid β-Peptides by Rueeger, Heinrich, Lueoend, Rainer, Rogel, Olivier, Rondeau, Jean-Michel, Möbitz, Henrik, Machauer, Rainer, Jacobson, Laura, Staufenbiel, Matthias, Desrayaud, Sandrine, Neumann, Ulf

“…Structure-based design of a series of cyclic hydroxyethylamine BACE1 inhibitors allowed the rational incorporation of prime- and nonprime-side fragments to a…”
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Type II Inhibitors Targeting CDK2 by Alexander, Leila T, Möbitz, Henrik, Drueckes, Peter, Savitsky, Pavel, Fedorov, Oleg, Elkins, Jonathan M, Deane, Charlotte M, Cowan-Jacob, Sandra W, Knapp, Stefan

“…Kinases can switch between active and inactive conformations of the ATP/Mg2+ binding motif DFG, which has been explored for the development of type I or type…”
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Paradoxical Increase of Permeability and Lipophilicity with the Increasing Topological Polar Surface Area within a Series of PRMT5 Inhibitors by Argikar, Upendra, Blatter, Markus, Bednarczyk, Dallas, Chen, Zhuoliang, Cho, Young Shin, Doré, Michaël, Dumouchel, Jennifer L., Ho, Samuel, Hoegenauer, Klemens, Kawanami, Toshio, Mathieu, Simon, Meredith, Erik, Möbitz, Henrik, Murphy, Stephen K., Parthasarathy, Saravanan, Soldermann, Carole Pissot, Santos, Jobette, Silver, Serena, Skolnik, Suzanne, Stojanovic, Aleksandar

“…An imidazolone → triazolone replacement addressed the limited passive permeability of a series of protein arginine methyl transferase 5 (PRMT5) inhibitors…”
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Discovery of Imidazoquinolines as a Novel Class of Potent, Selective, and in Vivo Efficacious Cancer Osaka Thyroid (COT) Kinase Inhibitors by Glatthar, Ralf, Stojanovic, Aleksandar, Troxler, Thomas, Mattes, Henri, Möbitz, Henrik, Beerli, Rene, Blanz, Joachim, Gassmann, Ernst, Drückes, Peter, Fendrich, Gabriele, Gutmann, Sascha, Martiny-Baron, Georg, Spence, Fiona, Hornfeld, Jeff, Peel, John Edmonson, Sparrer, Helmut

“…Cancer Osaka thyroid (COT) kinase is an important regulator of pro-inflammatory cytokines in macrophages. Thus, pharmacologic inhibition of COT should be a…”
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Challenges for the Discovery of Non‐Covalent WRN Helicase Inhibitors by Heuser, Alisa, Abdul Rahman, Wassim, Bechter, Elisabeth, Blank, Jutta, Buhr, Sylvia, Erdmann, Dirk, Fontana, Patrizia, Mermet‐Meillon, Fanny, Meyerhofer, Marco, Strang, Ross, Schrapp, Maxime, Zimmermann, Catherine, Cortes‐Cros, Marta, Möbitz, Henrik, Hamon, Jacques

“…The Werner Syndrome RecQ helicase (WRN) is a synthetic lethal target of interest for the treatment of cancers with microsatellite instability (MSI). Different…”
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Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor by Karpov, Alexei S, Amiri, Payman, Bellamacina, Cornelia, Bellance, Marie-Helene, Breitenstein, Werner, Daniel, Dylan, Denay, Regis, Fabbro, Doriano, Fernandez, Cesar, Galuba, Inga, Guerro-Lagasse, Stephanie, Gutmann, Sascha, Hinh, Linda, Jahnke, Wolfgang, Klopp, Julia, Lai, Albert, Lindvall, Mika K, Ma, Sylvia, Möbitz, Henrik, Pecchi, Sabina, Rummel, Gabriele, Shoemaker, Kevin, Trappe, Joerg, Voliva, Charles, Cowan-Jacob, Sandra W, Marzinzik, Andreas L

“…The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels…”
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New Potent DOT1L Inhibitors for in Vivo Evaluation in Mouse by Stauffer, Frédéric, Weiss, Andreas, Scheufler, Clemens, Möbitz, Henrik, Ragot, Christian, Beyer, Kim S, Calkins, Keith, Guthy, Daniel, Kiffe, Michael, Van Eerdenbrugh, Bernard, Tiedt, Ralph, Gaul, Christoph

“…In MLL-rearranged cancer cells, disruptor of telomeric silencing 1-like protein (DOT1L) is aberrantly recruited to ectopic loci leading to local…”
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Design Principles for Balancing Lipophilicity and Permeability in beyond Rule of 5 Space by Möbitz, Henrik

“…An ab initio conformational analysis of oral beyond Rule of 5 (bRo5) drugs was complemented with measured permeability and logP(octanol) to derive design…”
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Structural biology contributions to tyrosine kinase drug discovery by Cowan-Jacob, Sandra W, Möbitz, Henrik, Fabbro, Doriano

“…Successful kinase inhibitor drug discovery relies heavily on the structural knowledge of the interaction of inhibitors with the target. Structural biology of…”
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Nonclassical Zwitterions as a Design Principle to Reduce Lipophilicity without Impacting Permeability by Möbitz, Henrik, Dittrich, Birger, Rodde, Stephane, Strang, Ross

“…The ionization of bioactive molecules impacts many ADME-relevant physicochemical properties, in particular, solubility, lipophilicity, and permeability…”
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Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors by Rueeger, Heinrich, Rondeau, Jean-Michel, McCarthy, Clive, Möbitz, Henrik, Tintelnot-Blomley, Marina, Neumann, Ulf, Desrayaud, Sandrine

“…This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments…”
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Front Cover: Design Principles for Balancing Lipophilicity and Permeability in beyond Rule of 5 Space (ChemMedChem 5/2024) by Möbitz, Henrik

“…The Front Cover illustrates neutral TPSA as a novel design principle in bRo5 space. Neutral TPSA is polarity that doesn′t translate into polar surface area…”
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The ABC of protein kinase conformations by Möbitz, Henrik

“…Due to their involvement in human diseases, protein kinases are an important therapeutic target class. Conformation is a key concept for understanding how…”
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Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers by Papillon, Julien P. N, Nakajima, Katsumasa, Adair, Christopher D, Hempel, Jonathan, Jouk, Andriana O, Karki, Rajeshri G, Mathieu, Simon, Möbitz, Henrik, Ntaganda, Rukundo, Smith, Troy, Visser, Michael, Hill, Susan E, Hurtado, Felipe Kellermann, Chenail, Gregg, Bhang, Hyo-Eun C, Bric, Anka, Xiang, Kay, Bushold, Geoffrey, Gilbert, Tamara, Vattay, Anthony, Dooley, Julie, Costa, Emily A, Park, Isabel, Li, Ailing, Farley, David, Lounkine, Eugen, Yue, Q. Kimberley, Xie, Xiaoling, Zhu, Xiaoping, Kulathila, Raviraj, King, Daniel, Hu, Tiancen, Vulic, Katarina, Cantwell, John, Luu, Catherine, Jagani, Zainab

“…SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a…”
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Discovery of Novel Dot1L Inhibitors through a Structure-Based Fragmentation Approach by Chen, Chao, Zhu, Hugh, Stauffer, Frédéric, Caravatti, Giorgio, Vollmer, Susanne, Machauer, Rainer, Holzer, Philipp, Möbitz, Henrik, Scheufler, Clemens, Klumpp, Martin, Tiedt, Ralph, Beyer, Kim S, Calkins, Keith, Guthy, Daniel, Kiffe, Michael, Zhang, Jeff, Gaul, Christoph

“…Oncogenic MLL fusion proteins aberrantly recruit Dot1L, a histone methyltransferase, to ectopic loci, leading to local hypermethylation of H3K79 and…”
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Discovery of MAP855, an Efficacious and Selective MEK1/2 Inhibitor with an ATP-Competitive Mode of Action by Poddutoori, Ramulu, Aardalen, Kimberly, Aithal, Kiran, Barahagar, Sanjeev Surendranath, Belliappa, Charamanna, Bock, Mark, Chelur, Shekar, Gerken, Andrea, Gopinath, Sreevalsam, Gruenenfelder, Bjoern, Kiffe, Michael, Krishnaswami, Maithreyi, Langowski, John, Madapa, Sudharshan, Narayanan, Kishore, Pandit, Chetan, Panigrahi, Sunil Kumar, Perrone, Mark, Potakamuri, Ravi Kumar, Ramachandra, Murali, Ramanathan, Anuradha, Ramos, Rita, Sager, Emine, Samajdar, Susanta, Subramanya, Hosahalli S, Thimmasandra, Devaraja Seethappa, Venetsanakos, Eleni, Möbitz, Henrik

“…Mutations in MEK1/2 have been described as a resistance mechanism to BRAF/MEK inhibitor treatment. We report the discovery of a novel ATP-competitive MEK1/2…”
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Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket by Scheufler, Clemens, Möbitz, Henrik, Gaul, Christoph, Ragot, Christian, Be, Céline, Fernández, César, Beyer, Kim S, Tiedt, Ralph, Stauffer, Frédéric

“…Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein…”
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Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach by Möbitz, Henrik, Machauer, Rainer, Holzer, Philipp, Vaupel, Andrea, Stauffer, Frédéric, Ragot, Christian, Caravatti, Giorgio, Scheufler, Clemens, Fernandez, Cesar, Hommel, Ulrich, Tiedt, Ralph, Beyer, Kim S, Chen, Chao, Zhu, Hugh, Gaul, Christoph

“…Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the…”
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Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers by Ferretti, Stephane, Hamon, Jacques, de Kanter, Ruben, Scheufler, Clemens, Andraos-Rey, Rita, Barbe, Stephanie, Bechter, Elisabeth, Blank, Jutta, Bordas, Vincent, Dammassa, Ernesta, Decker, Andrea, Di Nanni, Noemi, Dourdoigne, Marion, Gavioli, Elena, Hattenberger, Marc, Heuser, Alisa, Hemmerlin, Christelle, Hinrichs, Jürgen, Kerr, Grainne, Laborde, Laurent, Jaco, Isabel, Núñez, Eloísa Jiménez, Martus, Hans-Joerg, Quadt, Cornelia, Reschke, Markus, Romanet, Vincent, Schaeffer, Fanny, Schoepfer, Joseph, Schrapp, Maxime, Strang, Ross, Voshol, Hans, Wartmann, Markus, Welly, Sarah, Zécri, Frédéric, Hofmann, Francesco, Möbitz, Henrik, Cortés-Cros, Marta

“…The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic…”
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Expanding the Opportunities for Modulating Kinase Targets with Allosteric Approaches by Mobitz, Henrik, Jahnke, Wolfgang, Cowan-Jacob, Sandra W

“…The need for novel approaches for targeting well-known protein families in drug discovery has been discussed for several years. There is a huge amount of…”
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