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Design, Synthesis, and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors
[Image: see text] In search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand’s performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical Society
2023
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388299/ https://www.ncbi.nlm.nih.gov/pubmed/37450644 http://dx.doi.org/10.1021/acs.jmedchem.3c00254 |
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| author | Ważyńska, Marta A. Butera, Roberto Requesens, Marta Plat, Annechien Zarganes-Tzitzikas, Tryfon Neochoritis, Constantinos G. Plewka, Jacek Skalniak, Lukasz Kocik-Krol, Justyna Musielak, Bogdan Magiera-Mularz, Katarzyna Rodriguez, Ismael Blok, Simon N. de Bruyn, Marco Nijman, Hans W. Elsinga, Philip H. Holak, Tad A. Dömling, Alexander |
| author_facet | Ważyńska, Marta A. Butera, Roberto Requesens, Marta Plat, Annechien Zarganes-Tzitzikas, Tryfon Neochoritis, Constantinos G. Plewka, Jacek Skalniak, Lukasz Kocik-Krol, Justyna Musielak, Bogdan Magiera-Mularz, Katarzyna Rodriguez, Ismael Blok, Simon N. de Bruyn, Marco Nijman, Hans W. Elsinga, Philip H. Holak, Tad A. Dömling, Alexander |
| author_sort | Ważyńska, Marta A. |
| collection | PubMed |
| description | [Image: see text] In search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand’s performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS1166. Subsequently, we modified both compounds to allow (18)F labeling that could be used for PET imaging. Radiolabeling, which is used in drug development and diagnosis, was applied to investigate the properties of those ligands and test them against tissue sections with diverse expression levels of PD-L1. We confirmed biological activity toward hPD-L1 for this inhibitor, comparable with BMS1166, while holding enhanced pharmacological properties. |
| format | Online Article Text |
| id | pubmed-10388299 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | American Chemical Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-103882992023-08-01 Design, Synthesis, and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors Ważyńska, Marta A. Butera, Roberto Requesens, Marta Plat, Annechien Zarganes-Tzitzikas, Tryfon Neochoritis, Constantinos G. Plewka, Jacek Skalniak, Lukasz Kocik-Krol, Justyna Musielak, Bogdan Magiera-Mularz, Katarzyna Rodriguez, Ismael Blok, Simon N. de Bruyn, Marco Nijman, Hans W. Elsinga, Philip H. Holak, Tad A. Dömling, Alexander J Med Chem [Image: see text] In search of a potent small molecular PD-L1 inhibitor, we designed and synthesized a compound based on a 2-hydroxy-4-phenylthiophene-3-carbonitrile moiety. Ligand’s performance was tested in vitro and compared side-by-side with a known PD-L1 antagonist with a proven bioactivity BMS1166. Subsequently, we modified both compounds to allow (18)F labeling that could be used for PET imaging. Radiolabeling, which is used in drug development and diagnosis, was applied to investigate the properties of those ligands and test them against tissue sections with diverse expression levels of PD-L1. We confirmed biological activity toward hPD-L1 for this inhibitor, comparable with BMS1166, while holding enhanced pharmacological properties. American Chemical Society 2023-07-14 /pmc/articles/PMC10388299/ /pubmed/37450644 http://dx.doi.org/10.1021/acs.jmedchem.3c00254 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
| spellingShingle | Ważyńska, Marta A. Butera, Roberto Requesens, Marta Plat, Annechien Zarganes-Tzitzikas, Tryfon Neochoritis, Constantinos G. Plewka, Jacek Skalniak, Lukasz Kocik-Krol, Justyna Musielak, Bogdan Magiera-Mularz, Katarzyna Rodriguez, Ismael Blok, Simon N. de Bruyn, Marco Nijman, Hans W. Elsinga, Philip H. Holak, Tad A. Dömling, Alexander Design, Synthesis, and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 Antagonist and Its Comparison to Available Small Molecular PD-L1 Inhibitors |
| title | Design, Synthesis,
and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile
as PD-L1 Antagonist and Its Comparison to Available Small Molecular
PD-L1 Inhibitors |
| title_full | Design, Synthesis,
and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile
as PD-L1 Antagonist and Its Comparison to Available Small Molecular
PD-L1 Inhibitors |
| title_fullStr | Design, Synthesis,
and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile
as PD-L1 Antagonist and Its Comparison to Available Small Molecular
PD-L1 Inhibitors |
| title_full_unstemmed | Design, Synthesis,
and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile
as PD-L1 Antagonist and Its Comparison to Available Small Molecular
PD-L1 Inhibitors |
| title_short | Design, Synthesis,
and Biological Evaluation of 2-Hydroxy-4-phenylthiophene-3-carbonitrile
as PD-L1 Antagonist and Its Comparison to Available Small Molecular
PD-L1 Inhibitors |
| title_sort | design, synthesis,
and biological evaluation of 2-hydroxy-4-phenylthiophene-3-carbonitrile
as pd-l1 antagonist and its comparison to available small molecular
pd-l1 inhibitors |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388299/ https://www.ncbi.nlm.nih.gov/pubmed/37450644 http://dx.doi.org/10.1021/acs.jmedchem.3c00254 |
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