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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
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
Descripción
Sumario:[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.

Ejemplares similares