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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.
Wazynska, 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.
Afiliación
  • Wazynska MA; Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Butera R; Department of Drug Design, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
  • Requesens M; Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Plat A; Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Zarganes-Tzitzikas T; Centre for Medicines Discovery, Nuffield Department of Medicine, Alzheimer's Research UK Oxford Drug Discovery Institute, NDM Research Building, Roosevelt Drive, OX3 7FZ Oxford, U.K.
  • Neochoritis CG; Department of Chemistry, University of Crete, Voutes, 70013 Heraklion, Greece.
  • Plewka J; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • Skalniak L; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • Kocik-Krol J; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • Musielak B; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Prof. St. Lojasiewicz St 11, 30-348 Krakow, Poland.
  • Magiera-Mularz K; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • Rodriguez I; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • Blok SN; Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland.
  • de Bruyn M; Doctoral School of Exact and Natural Sciences, Jagiellonian University, Prof. St. Lojasiewicz St 11, 30-348 Krakow, Poland.
  • Nijman HW; Department of Nuclear Medicine and MolecularImaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Elsinga PH; Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Holak TA; Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
  • Dömling A; Department of Nuclear Medicine and MolecularImaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
J Med Chem ; 66(14): 9577-9591, 2023 07 27.
Article en En | MEDLINE | ID: mdl-37450644
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.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígeno B7-H1 / Inhibidores de Puntos de Control Inmunológico Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Antígeno B7-H1 / Inhibidores de Puntos de Control Inmunológico Idioma: En Revista: J Med Chem Asunto de la revista: QUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Países Bajos