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
<p>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 BM...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2023
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| _version_ | 1797113026466283520 |
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| author | Ważyńska, MA Butera, R Requesens, M Plat, A Zarganis-Tzitzikas, T Neochoritis, CG Plewka, J Skalniak, L Kocik-Krol, J Musielak, B Magiera-Mularz, K Rodriguez, I Blok, SN de Bruyn, M Nijman, HW Elsinga, PH Holak, TA Dömling, A |
| author_facet | Ważyńska, MA Butera, R Requesens, M Plat, A Zarganis-Tzitzikas, T Neochoritis, CG Plewka, J Skalniak, L Kocik-Krol, J Musielak, B Magiera-Mularz, K Rodriguez, I Blok, SN de Bruyn, M Nijman, HW Elsinga, PH Holak, TA Dömling, A |
| author_sort | Ważyńska, MA |
| collection | OXFORD |
| description | <p>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 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.</p> |
| first_indexed | 2024-04-09T03:57:54Z |
| format | Journal article |
| id | oxford-uuid:70e8f1f9-6366-4501-b627-ebf7be1e62f8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-09T03:57:54Z |
| publishDate | 2023 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:70e8f1f9-6366-4501-b627-ebf7be1e62f82024-03-28T11:47:58ZDesign, synthesis, and biological evaluation of 2-hydroxy-4-phenylthiophene-3-carbonitrile as PD-L1 antagonist and its comparison to available small molecular PD-L1 inhibitorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:70e8f1f9-6366-4501-b627-ebf7be1e62f8EnglishSymplectic ElementsAmerican Chemical Society2023Ważyńska, MAButera, RRequesens, MPlat, AZarganis-Tzitzikas, TNeochoritis, CGPlewka, JSkalniak, LKocik-Krol, JMusielak, BMagiera-Mularz, KRodriguez, IBlok, SNde Bruyn, MNijman, HWElsinga, PHHolak, TADömling, A<p>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 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.</p> |
| spellingShingle | Ważyńska, MA Butera, R Requesens, M Plat, A Zarganis-Tzitzikas, T Neochoritis, CG Plewka, J Skalniak, L Kocik-Krol, J Musielak, B Magiera-Mularz, K Rodriguez, I Blok, SN de Bruyn, M Nijman, HW Elsinga, PH Holak, TA Dömling, A 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
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