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Cited by 422

The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.

Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

Open access
Zak, Krzysztof M., Grudnik, Przemyslaw, Guzik, Katarzyna, Zieba, Bartosz J., Musielak, Bogdan, Dömling, Alexander, Dubin, Grzegorz, Holak, Tad A.·2016·Oncotarget
DOI 10.18632/oncotarget.8730
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Abstract

// Krzysztof M. Zak 1,2 , Przemyslaw Grudnik 2 , Katarzyna Guzik 3 , Bartosz J. Zieba 1,3 , Bogdan Musielak 3 , Alexander Dömling 4 , Grzegorz Dubin 1,2 and Tad A. Holak 1,3,5 1 Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa, Krakow, Poland 2 Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa, Krakow, Poland 3 Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Ingardena, Krakow, Poland 4 Department for Drug Design, University of Groningen, A. Deusinglaan , Groningen, The Netherlands 5 Max Planck Institute for Biochemistry, Am Klopferspitz, Martinsried, Germany Correspondence to: Grzegorz Dubin, email: // Tad A. Holak, email: // Keywords : immunotherapy, checkpoint inhibitor, small molecule, X-ray structure Received : March 30, 2016 Accepted : March 31, 2016 Published : April 13, 2016 Abstract Targeting the PD-1/PD-L1 immunologic checkpoint with monoclonal antibodies has provided unprecedented results in cancer treatment in the recent years. Development of chemical inhibitors for this pathway lags the antibody development because of insufficient structural information. The first nonpeptidic chemical inhibitors that target the PD-1/PD-L1 interaction have only been recently disclosed by Bristol-Myers Squibb. Here, we show that these small-molecule compounds bind directly to PD-L1 and that they potently block PD-1 binding. Structural studies reveal a dimeric protein complex with a single small molecule which stabilizes the dimer thus occluding the PD-1 interaction surface of PD-L1s. The small-molecule interaction “hot spots” on PD-L1 surfaces suggest approaches for the PD-1/PD-L1 antagonist drug discovery.

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Metadata

Authors
Zak, K. M., Grudnik, P., Guzik, K., Zieba, B. J., Musielak, B., Dömling, A., Dubin, G., & Holak, T. A.
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-04-13
Volume
7
Issue
21
Pages
30323-30335
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.8730
OpenAlex
W2338150527
Cited by
422
References
38
FWCI
13.91
Type
journal article
Language
en
Open access
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CoChat. (2026). Citation check: Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). https://app.cochat.ai/papers/10.18632/oncotarget.8730
The paper
Zak, K. M., Grudnik, P., Guzik, K., Zieba, B. J., Musielak, B., Dömling, A., Dubin, G., & Holak, T. A. (2016). Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1). Oncotarget. https://doi.org/10.18632/oncotarget.8730

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