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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
MA. Ważyńska, R. Butera, M. Requesens, A. Plat, T. Zarganes-Tzitzikas, CG. Neochoritis, J. Plewka, L. Skalniak, J. Kocik-Krol, B. Musielak, K. Magiera-Mularz, I. Rodriguez, SN. Blok, M. de Bruyn, HW. Nijman, PH. Elsinga, TA. Holak, A. Dömling
Journal of medicinal chemistry.
2023 ;
66 (14) :
9577-9591.
[pub] 20230714
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Perzistentní odkaz
https://www.medvik.cz/link/bmc23016814
- MeSH
- antigeny CD274 * MeSH
- inhibitory kontrolních bodů * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 18F 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.
Department of Chemistry University of Crete Voutes 70013 Heraklion Greece
Department of Drug Design University of Groningen A Deusinglaan 1 9713 AV Groningen The Netherlands
Citace poskytuje Crossref.org
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- $a Ważyńska, Marta A $u Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands $1 https://orcid.org/0000000216267450
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