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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.

ABSTRACT: 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.

SUBMITTER: Wazynska MA 

PROVIDER: S-EPMC10388299 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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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.

Ważyńska Marta A MA   Butera Roberto R   Requesens Marta M   Plat Annechien A   Zarganes-Tzitzikas Tryfon T   Neochoritis Constantinos G CG   Plewka Jacek J   Skalniak Lukasz L   Kocik-Krol Justyna J   Musielak Bogdan B   Magiera-Mularz Katarzyna K   Rodriguez Ismael I   Blok Simon N SN   de Bruyn Marco M   Nijman Hans W HW   Elsinga Philip H PH   Holak Tad A TA   Dömling Alexander A  

Journal of medicinal chemistry 20230714 14

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 <sup>18</sup>F labeling that could be used for PET imaging. Radiolabeling, which is used in drug development and diagnosis, was applied to investigate the propert  ...[more]

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