Tags

Type your tag names separated by a space and hit enter

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)M

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.

Authors+Show Affiliations

Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. katarzyna.guzik01@gmail.com.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. marcintomala87@gmail.com.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. damian.muszak@doctoral.uj.edu.pl.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. madzienkakonieczny@gmail.com.Recepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, Poland. ola.hec@op.pl.Recepton sp. z o.o, Michala Bobrzynskiego 14, 30-348 Krakow, Poland. urszula.blaszkiewicz@receptonbiotech.com.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. pustula.marcin@gmail.com.Department for Drug Design, University of Groningen, A. Deusinglaan 9, AV 9713 Groningen, The Netherlands. r.butera@rug.nl.Department for Drug Design, University of Groningen, A. Deusinglaan 9, AV 9713 Groningen, The Netherlands. a.s.s.domling@rug.nl.Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, 30-387 Krakow, Poland. tadholak@uj.edu.pl.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31151293

Citation

Guzik, Katarzyna, et al. "Development of the Inhibitors That Target the PD-1/PD-L1 Interaction-A Brief Look at Progress On Small Molecules, Peptides and Macrocycles." Molecules (Basel, Switzerland), vol. 24, no. 11, 2019.
Guzik K, Tomala M, Muszak D, et al. 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).
Guzik, K., Tomala, M., Muszak, D., Konieczny, M., Hec, A., Błaszkiewicz, U., ... Holak, T. A. (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 (Basel, Switzerland), 24(11), doi:10.3390/molecules24112071.
Guzik K, et al. 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 May 30;24(11) PubMed PMID: 31151293.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Development of the Inhibitors that Target the PD-1/PD-L1 Interaction-A Brief Look at Progress on Small Molecules, Peptides and Macrocycles. AU - Guzik,Katarzyna, AU - Tomala,Marcin, AU - Muszak,Damian, AU - Konieczny,Magdalena, AU - Hec,Aleksandra, AU - Błaszkiewicz,Urszula, AU - Pustuła,Marcin, AU - Butera,Roberto, AU - Dömling,Alexander, AU - Holak,Tad A, Y1 - 2019/05/30/ PY - 2019/05/13/received PY - 2019/05/27/revised PY - 2019/05/28/accepted PY - 2019/6/2/entrez PY - 2019/6/4/pubmed PY - 2019/6/4/medline KW - PD-1/PD-L1 pathway KW - cancer immunotherapy KW - cocrystal structures KW - lead optimization KW - peptide-based and small synthetic molecule inhibitors KW - rational drug design KW - scaffold hopping KW - structure-activity relationship JF - Molecules (Basel, Switzerland) JO - Molecules VL - 24 IS - 11 N2 - 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/31151293/Development_of_the_Inhibitors_that_Target_the_PD-1/PD-L1_Interaction-A_Brief_Look_at_Progress_on_Small_Molecules,_Peptides_and_Macrocycles L2 - http://www.mdpi.com/resolver?pii=molecules24112071 DB - PRIME DP - Unbound Medicine ER -