دورية أكاديمية
Development of Highly Potent and Selective Covalent FGFR4 Inhibitors Based on S N Ar Electrophiles.
| العنوان: | Development of Highly Potent and Selective Covalent FGFR4 Inhibitors Based on S |
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| المؤلفون: | Schwarz M; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany., Kurkunov M; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany., Wittlinger F; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany., Rudalska R; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany.; Department of Medical Oncology and Pneumology, University Hospital Tübingen, 72076 Tübingen, Germany., Wang G; German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Structural Genomics Consortium (SGC), Buchmann Institute for Molecular Life Sciences, Goethe-University Frankfurt, Max-von Laue Str. 15, 60438 Frankfurt am Main, Germany.; Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von Laue Str. 9, 60438 Frankfurt am Main, Germany., Schwalm MP; German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Structural Genomics Consortium (SGC), Buchmann Institute for Molecular Life Sciences, Goethe-University Frankfurt, Max-von Laue Str. 15, 60438 Frankfurt am Main, Germany.; Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von Laue Str. 9, 60438 Frankfurt am Main, Germany., Rasch A; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany., Wagner B; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany., Laufer SA; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany.; Tübingen Center for Academic Drug Discovery & Development (TüCAD2), 72076 Tübingen, Germany., Knapp S; German Cancer Research Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Structural Genomics Consortium (SGC), Buchmann Institute for Molecular Life Sciences, Goethe-University Frankfurt, Max-von Laue Str. 15, 60438 Frankfurt am Main, Germany.; Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von Laue Str. 9, 60438 Frankfurt am Main, Germany., Dauch D; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany.; Department of Medical Oncology and Pneumology, University Hospital Tübingen, 72076 Tübingen, Germany.; Tübingen Center for Academic Drug Discovery & Development (TüCAD2), 72076 Tübingen, Germany., Gehringer M; Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmaceutical Sciences, Eberhard Karls University Tübingen, 72076 Tübingen, Germany.; Cluster of Excellence iFIT (EXC 2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, 72076 Tübingen, Germany. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2024 Apr 25; Vol. 67 (8), pp. 6549-6569. Date of Electronic Publication: 2024 Apr 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Receptor, Fibroblast Growth Factor, Type 4*/antagonists & inhibitors , Receptor, Fibroblast Growth Factor, Type 4*/metabolism , Protein Kinase Inhibitors*/pharmacology , Protein Kinase Inhibitors*/chemistry , Protein Kinase Inhibitors*/chemical synthesis, Humans ; Structure-Activity Relationship ; Microsomes, Liver/metabolism |
| مستخلص: | Fibroblast growth factor receptor 4 (FGFR4) is thought to be a driver in several cancer types, most notably in hepatocellular carcinoma. One way to achieve high potency and isoform selectivity for FGFR4 is covalently targeting a rare cysteine (C552) in the hinge region of its kinase domain that is not present in other FGFR family members (FGFR1-3). Typically, this cysteine is addressed via classical acrylamide electrophiles. We demonstrate that noncanonical covalent "warheads" based on nucleophilic aromatic substitution (S |
| المشرفين على المادة: | EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 4) 0 (Protein Kinase Inhibitors) EC 2.7.10.1 (FGFR4 protein, human) |
| تواريخ الأحداث: | Date Created: 20240411 Date Completed: 20240425 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| DOI: | 10.1021/acs.jmedchem.3c02483 |
| PMID: | 38604131 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.3c02483 |