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

Guzik, Katarzyna; Tomala, Marcin; Muszak, Damian; Konieczny, Magdalena; Hec, Aleksandra; Błaszkiewicz, Urszula; Pustuła, Marcin; Butera, Roberto; Dömling, Alexander; Holak, Tad A.

doi:10.3390/molecules24112071

Submit to this Journal Review for this Journal Edit a Special Issue

Article Menu

...

Open AccessFeature PaperReview

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

^1,*

¹,

²,

²,

³,

³ and

Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland

Recepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, Poland

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)

Abstract

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

▼ Show Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 1248 KiB)

Share and Cite

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

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

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

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI