Computationally driven discovery of SARS-CoV-2 Mpro inhibitors: from design to experimental validation

Autor: Khoury, L. El, Jing, Z., Cuzzolin, A., Deplano, A., Loco, D., Sattarov, B., Hédin, F., Wendeborn, S., Ho, C., Ahdab, D. El, Inizan, T. Jaffrelot, Sturlese, M., Sosic, A., Volpiana, M., Lugato, A., Barone, M., Gatto, B., Macchia, M. Ludovica, Bellanda, M., Battistutta, R., Salata, C., Kondratov, I., Iminov, R., Khairulin, A., Mykhalonok, Y., Pochepko, A., Chashka-Ratushnyi, V., Kos, I., Moro, S., Montes, M., Ren, P., Ponder, J. W., Lagardère, L., Piquemal, J. -P., Sabbadin, D.

Publikováno v: Chem. Sci., 2022,13, 3674-3687

We report a fast-track computationally-driven discovery of new SARS-CoV2 Main Protease (M$^{pro}$) inhibitors whose potency range from mM for initial non-covalent ligands to sub-$\mu$M for the final covalent compound (IC50=830 +/- 50 nM). The project

Externí odkaz: http://arxiv.org/abs/2110.05427

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An engineered cereblon optimized for high throughput screening and molecular glue discovery.

Autor: Bailey HJ; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany., Eisert J; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany., Kazi R; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany., Gerhartz J; Institute of Structural Biology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany., Pieńkowska DE; Institute of Structural Biology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany., Dressel I; Institute of Structural Biology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany., Vollrath J; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany; Max Planck Institute of Biophysics, IMPRS on Cellular Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany., Kondratov I; Enamine Ltd., Winston Churchill Street 78, 02094 Kyiv, Ukraine; Enamine Germany GmbH, Industriepark Hoechst, G837, 65926 Frankfurt am Main, Germany; V. P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Akademik Kukhar Street 1, 02094 Kyiv, Ukraine., Matviyuk T; Enamine Ltd., Winston Churchill Street 78, 02094 Kyiv, Ukraine., Tolmachova N; Enamine Ltd., Winston Churchill Street 78, 02094 Kyiv, Ukraine., Shah VJ; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany., Giuliani G; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany., Mosler T; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany., Geiger TM; Institute of Structural Biology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany., Esteves AM; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal., Santos SP; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal., Sousa RL; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal., Bandeiras TM; iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, Portugal., Leibrock EM; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany., Bauer U; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany., Leuthner B; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany., Langer JD; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany; Max Planck Institute for Brain Research, Max-von-Laue-Strasse 4, 60439 Frankfurt am Main, Germany., Wegener AA; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany., Nowak RP; Institute of Structural Biology, University of Bonn, Venusberg Campus 1, 53127 Bonn, Germany., Sorrell FJ; Merck Healthcare KGaA, Discovery and Development Technologies, Frankfurter Straße 250, 64293 Darmstadt, Germany. Electronic address: fiona.sorrell@merckgroup.com., Dikic I; Institute of Biochemistry II, Medical Faculty, Goethe-University, Frankfurt am Main and Buchmann Institute for Molecular Life Sciences, Frankfurt am Main, Germany; Max Planck Institute of Biophysics, Max-von-Laue-Strasse 3, 60439 Frankfurt am Main, Germany. Electronic address: dikic@biochem2.uni-frankfurt.de.

Publikováno v: Cell chemical biology [Cell Chem Biol] 2024 Nov 20. Date of Electronic Publication: 2024 Nov 20.

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The synthesis of cis- and trans-3-(4-hydroxyphenyl)cyclobutanecarboxylic acids and the study of their derivatives as GPR-40 receptor ligands

Autor: Feskov, I. O., Kondratov, I. S., Kuchkovska, Yu. O., Naumchyk, V. S., Onopchenko, O. V., Grygorenko, O. O.

Publikováno v: Журнал органічної та фармацевтичної хімії; Том 18, № 4(72) (2020); 14-22
Journal of Organic and Pharmaceutical Chemistry; Том 18, № 4(72) (2020); 14-22
Журнал органической и фармацевтической химии; Том 18, № 4(72) (2020); 14-22

Aim. To synthesize cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarboxylic acid and evaluate the biological activity of their derivatives against GPR-40.Results and discussion. Cis- and trans-isomers of 3-(4-hydroxyphenyl)cyclobutanecarbox

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=scientific_p::8949f21f20cd29ab0e3ebcd5bd880d16
http://ophcj.nuph.edu.ua/article/view/ophcj.20.210383