Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles
Cancer immunotherapy based on antibodies targeting the immune checkpoint PD-1/PD-L1 pathway has seen unprecedented clinical responses and constitutes the new paradigm in cancer therapy. The antibody-based immunotherapies have several limitations such as high production cost of the antibodies or thei...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/11/2071 |
| _version_ | 1818518950305071104 |
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| author | Katarzyna Guzik Marcin Tomala Damian Muszak Magdalena Konieczny Aleksandra Hec Urszula Błaszkiewicz Marcin Pustuła Roberto Butera Alexander Dömling Tad A. Holak |
| author_facet | Katarzyna Guzik Marcin Tomala Damian Muszak Magdalena Konieczny Aleksandra Hec Urszula Błaszkiewicz Marcin Pustuła Roberto Butera Alexander Dömling Tad A. Holak |
| author_sort | Katarzyna Guzik |
| collection | DOAJ |
| description | Cancer immunotherapy based on antibodies targeting the immune checkpoint PD-1/PD-L1 pathway has seen unprecedented clinical responses and constitutes the new paradigm in cancer therapy. The antibody-based immunotherapies have several limitations such as high production cost of the antibodies or their long half-life. Small-molecule inhibitors of the PD-1/PD-L1 interaction have been highly anticipated as a promising alternative or complementary therapeutic to the monoclonal antibodies (mAbs). Currently, the field of developing anti-PD-1/PD-L1 small-molecule inhibitors is intensively explored. In this paper, we review anti-PD-1/PD-L1 small-molecule and peptide-based inhibitors and discuss recent structural and preclinical/clinical aspects of their development. Discovery of the therapeutics based on small-molecule inhibitors of the PD-1/PD-L1 interaction represents a promising but challenging perspective in cancer treatment. |
| first_indexed | 2024-12-11T01:17:15Z |
| format | Article |
| id | doaj.art-f8845f78c3864840bfe4b4868e458431 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-11T01:17:15Z |
| publishDate | 2019-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f8845f78c3864840bfe4b4868e4584312022-12-22T01:25:50ZengMDPI AGMolecules1420-30492019-05-012411207110.3390/molecules24112071molecules24112071Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and MacrocyclesKatarzyna Guzik0Marcin Tomala1Damian Muszak2Magdalena Konieczny3Aleksandra Hec4Urszula Błaszkiewicz5Marcin Pustuła6Roberto Butera7Alexander Dömling8Tad A. Holak9Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandFaculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandFaculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandFaculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandRecepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, PolandRecepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, PolandFaculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandDepartment for Drug Design, University of Groningen, A. Deusinglaan 9, AV 9713 Groningen, The NetherlandsDepartment for Drug Design, University of Groningen, A. Deusinglaan 9, AV 9713 Groningen, The NetherlandsFaculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, PolandCancer immunotherapy based on antibodies targeting the immune checkpoint PD-1/PD-L1 pathway has seen unprecedented clinical responses and constitutes the new paradigm in cancer therapy. The antibody-based immunotherapies have several limitations such as high production cost of the antibodies or their long half-life. Small-molecule inhibitors of the PD-1/PD-L1 interaction have been highly anticipated as a promising alternative or complementary therapeutic to the monoclonal antibodies (mAbs). Currently, the field of developing anti-PD-1/PD-L1 small-molecule inhibitors is intensively explored. In this paper, we review anti-PD-1/PD-L1 small-molecule and peptide-based inhibitors and discuss recent structural and preclinical/clinical aspects of their development. Discovery of the therapeutics based on small-molecule inhibitors of the PD-1/PD-L1 interaction represents a promising but challenging perspective in cancer treatment.https://www.mdpi.com/1420-3049/24/11/2071peptide-based and small synthetic molecule inhibitorslead optimizationscaffold hoppingPD-1/PD-L1 pathwayrational drug designcancer immunotherapycocrystal structuresstructure-activity relationship |
| spellingShingle | Katarzyna Guzik Marcin Tomala Damian Muszak Magdalena Konieczny Aleksandra Hec Urszula Błaszkiewicz Marcin Pustuła Roberto Butera Alexander Dömling Tad A. Holak Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles Molecules peptide-based and small synthetic molecule inhibitors lead optimization scaffold hopping PD-1/PD-L1 pathway rational drug design cancer immunotherapy cocrystal structures structure-activity relationship |
| title | Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles |
| title_full | Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles |
| title_fullStr | Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles |
| title_full_unstemmed | Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles |
| title_short | Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles |
| title_sort | development of the inhibitors that target the pd 1 pd l1 interaction a brief look at progress on small molecules peptides and macrocycles |
| topic | peptide-based and small synthetic molecule inhibitors lead optimization scaffold hopping PD-1/PD-L1 pathway rational drug design cancer immunotherapy cocrystal structures structure-activity relationship |
| url | https://www.mdpi.com/1420-3049/24/11/2071 |
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