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Review

Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles

1
Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland
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Recepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, Poland
3
Department for Drug Design, University of Groningen, A. Deusinglaan 9, AV 9713 Groningen, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Pawel Kafarski
Molecules 2019, 24(11), 2071; https://doi.org/10.3390/molecules24112071
Received: 13 May 2019 / Revised: 27 May 2019 / Accepted: 28 May 2019 / Published: 30 May 2019
(This article belongs to the Special Issue Design and Synthesis of Bioactive Compounds)
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. View Full-Text
Keywords: 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 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
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MDPI and ACS Style

Guzik, K.; Tomala, M.; Muszak, D.; Konieczny, M.; Hec, A.; Błaszkiewicz, U.; Pustuła, M.; Butera, R.; Dömling, A.; Holak, T.A. Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles. Molecules 2019, 24, 2071. https://doi.org/10.3390/molecules24112071

AMA Style

Guzik K, Tomala M, Muszak D, Konieczny M, Hec A, Błaszkiewicz U, Pustuła M, Butera R, Dömling A, Holak TA. Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles. Molecules. 2019; 24(11):2071. https://doi.org/10.3390/molecules24112071

Chicago/Turabian Style

Guzik, Katarzyna, Marcin Tomala, Damian Muszak, Magdalena Konieczny, Aleksandra Hec, Urszula Błaszkiewicz, Marcin Pustuła, Roberto Butera, Alexander Dömling, and Tad A. Holak. 2019. "Development of the Inhibitors That Target the PD-1/PD-L1 Interaction—A Brief Look at Progress on Small Molecules, Peptides and Macrocycles" Molecules 24, no. 11: 2071. https://doi.org/10.3390/molecules24112071

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