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

Marta A Ważyńska, Roberto Butera, Marta Requesens, Annechien Plat, Tryfon Zarganes-Tzitzikas, Constantinos G Neochoritis, Jacek Plewka, Lukasz Skalniak, Justyna Kocik-Krol, Bogdan Musielak, Katarzyna Magiera-Mularz, Ismael Rodriguez, Simon N Blok, Marco de Bruyn, Hans W Nijman, Philip H Elsinga, Tad A Holak, Alexander Dömling*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
40 Downloads (Pure)


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.

Original languageEnglish
Pages (from-to)9577-9591
Number of pages15
JournalJournal of Medicinal Chemistry
Issue number14
Publication statusPublished - 27-Jul-2023


  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen

Cite this