دورية أكاديمية
Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction-Reconstruction and Fragment-Growing Approach
| العنوان: | Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction-Reconstruction and Fragment-Growing Approach |
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| المؤلفون: | Iannelli, Giulia, Milite, Ciro, Marechal, Nils, Cura, Vincent, Bonnefond, Luc, Troffer-Charlier, Nathalie, Feoli, Alessandra, Rescigno, Donatella, Wang, Yalong, Cipriano, Alessandra, Viviano, Monica, Bedford, Mark, Cavarelli, Jean, Castellano, Sabrina, Sbardella, Gianluca |
| المساهمون: | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | ISSN: 0022-2623. |
| بيانات النشر: | HAL CCSD American Chemical Society |
| سنة النشر: | 2022 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology |
| الوصف: | Protein arginine methyltransferases (PRMTs) are important therapeutic targets, playing a crucial role in the regulation of many cellular processes and being linked to many diseases. Yet, there is still much to be understood regarding their functions and the biological pathways in which they are involved, as well as on the structural requirements that could drive the development of selective modulators of PRMT activity. Here we report a deconstruction-reconstruction approach that, starting from a series of type I PRMT inhibitors previously identified by us, allowed for the identification of potent and selective inhibitors of PRMT4, which regardless of the low cell permeability show an evident reduction of arginine methylation levels in MCF7 cells and a marked reduction of proliferation. We also report crystal structures with various PRMTs supporting the observed specificity and selectivity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-04116086; https://hal.science/hal-04116086Test; https://hal.science/hal-04116086/documentTest; https://hal.science/hal-04116086/file/islandora_163785.pdfTest |
| DOI: | 10.1021/acs.jmedchem.2c00252 |
| الإتاحة: | https://doi.org/10.1021/acs.jmedchem.2c00252Test https://hal.science/hal-04116086Test https://hal.science/hal-04116086/documentTest https://hal.science/hal-04116086/file/islandora_163785.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.D7DEEB7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.2c00252 |
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