Fragment-based screening of programmed death ligand 1 (PD-L1)

Perry, Evan; Mills, Jonathan J.; Zhao, Bin; Wang, Feng; Sun, Qi; Christov, Plamen P.; Tarr, James C.; Rietz, Tyson A.; Olejniczak, Edward T.; Lee, Taekyu; Fesik, Stephen

doi:10.1016/j.bmcl.2019.01.028

Title: Fragment-based screening of programmed death ligand 1 (PD-L1)

Journal Article · 23 January 2019 · Bioorganic and Medicinal Chemistry Letters

DOI: https://doi.org/10.1016/j.bmcl.2019.01.028 · OSTI ID:1544853

Perry, Evan ^[1]; Mills, Jonathan J. ^[1]; Zhao, Bin ^[1]; Wang, Feng ^[1]; Sun, Qi ^[1]; Christov, Plamen P. ^[1]; Tarr, James C. ^[1]; Rietz, Tyson A. ^[1]; Olejniczak, Edward T. ^[1]; Lee, Taekyu ^[1];

^[1]

Vanderbilt Univ., Nashville, TN (United States)

The PD-1 immune checkpoint pathway is a highly validated target for cancer immunotherapy. Despite the potential advantages of small molecule inhibitors over antibodies, the discovery of small molecule checkpoint inhibitors has lagged behind. To discover small molecule inhibitors of the PD-1 pathway, we have utilized a fragment-based approach. Small molecules were identified that bind to PD-L1 and crystal structures of these compounds bound to PD-L1 were obtained.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Contributing Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1544853

Journal Information:: Bioorganic and Medicinal Chemistry Letters, Journal Name: Bioorganic and Medicinal Chemistry Letters Journal Issue: 6 Vol. 29; ISSN 0960-894X

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (29)

Bioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint Magiera-Mularz, Katarzyna; Skalniak, Lukasz; Zak, Krzysztof M. Angewandte Chemie International Edition, Vol. 56, Issue 44 https://doi.org/10.1002/anie.201707707	journal	September 2017
Fragment-based drug discovery using NMR spectroscopy Harner, Mary J.; Frank, Andreas O.; Fesik, Stephen W. Journal of Biomolecular NMR, Vol. 56, Issue 2 https://doi.org/10.1007/s10858-013-9740-z	journal	May 2013
Immune-Related Adverse Events Associated with Immune Checkpoint Inhibitors Day, Daphne; Hansen, Aaron R. BioDrugs, Vol. 30, Issue 6 https://doi.org/10.1007/s40259-016-0204-3	journal	November 2016
Hallmarks of Cancer: The Next Generation Hanahan, Douglas; Weinberg, Robert A. Cell, Vol. 144, Issue 5 https://doi.org/10.1016/j.cell.2011.02.013	journal	March 2011
Immune-related adverse events with immune checkpoint blockade: a comprehensive review Michot, J. M.; Bigenwald, C.; Champiat, S. European Journal of Cancer, Vol. 54 https://doi.org/10.1016/j.ejca.2015.11.016	journal	February 2016
Structure of the Complex of Human Programmed Death 1, PD-1, and Its Ligand PD-L1 Zak, Krzysztof M.; Kitel, Radoslaw; Przetocka, Sara Structure, Vol. 23, Issue 12 https://doi.org/10.1016/j.str.2015.09.010	journal	December 2015
Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2 Zak, Krzysztof M.; Grudnik, Przemyslaw; Magiera, Katarzyna Structure, Vol. 25, Issue 8 https://doi.org/10.1016/j.str.2017.06.011	journal	August 2017
Small-Molecule Inhibitors of the Programmed Cell Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) Interaction via Transiently Induced Protein States and Dimerization of PD-L1 Guzik, Katarzyna; Zak, Krzysztof M.; Grudnik, Przemyslaw Journal of Medicinal Chemistry, Vol. 60, Issue 13 https://doi.org/10.1021/acs.jmedchem.7b00293	journal	June 2017
An NMR-Based Antagonist Induced Dissociation Assay for Targeting the Ligand−Protein and Protein−Protein Interactions in Competition Binding Experiments Krajewski, Marcin; Rothweiler, Ulli; D'Silva, Loyola Journal of Medicinal Chemistry, Vol. 50, Issue 18 https://doi.org/10.1021/jm070365v	journal	September 2007
Discovery of a Potent Stapled Helix Peptide That Binds to the 70N Domain of Replication Protein A Frank, Andreas O.; Vangamudi, Bhavatarini; Feldkamp, Michael D. Journal of Medicinal Chemistry, Vol. 57, Issue 6 https://doi.org/10.1021/jm401730y	journal	February 2014
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients Herbst, Roy S.; Soria, Jean-Charles; Kowanetz, Marcin Nature, Vol. 515, Issue 7528 https://doi.org/10.1038/nature14011	journal	November 2014
Comparing antibody and small-molecule therapies for cancer Imai, Kohzoh; Takaoka, Akinori Nature Reviews Cancer, Vol. 6, Issue 9 https://doi.org/10.1038/nrc1913	journal	September 2006
Antibody therapy of cancer Scott, Andrew M.; Wolchok, Jedd D.; Old, Lloyd J. Nature Reviews Cancer, Vol. 12, Issue 4 https://doi.org/10.1038/nrc3236	journal	March 2012
The blockade of immune checkpoints in cancer immunotherapy Pardoll, Drew M. Nature Reviews Cancer, Vol. 12, Issue 4 https://doi.org/10.1038/nrc3239	journal	March 2012
Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging Maute, Roy L.; Gordon, Sydney R.; Mayer, Aaron T. Proceedings of the National Academy of Sciences, Vol. 112, Issue 47 https://doi.org/10.1073/pnas.1519623112	journal	November 2015
Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade Iwai, Y.; Ishida, M.; Tanaka, Y. Proceedings of the National Academy of Sciences, Vol. 99, Issue 19 https://doi.org/10.1073/pnas.192461099	journal	September 2002
Inhibitors of programmed cell death 1 (PD-1): a patent review (2010-2015) Zarganes-Tzitzikas, Tryfon; Konstantinidou, Markella; Gao, Yongzhi Expert Opinion on Therapeutic Patents, Vol. 26, Issue 9 https://doi.org/10.1080/13543776.2016.1206527	journal	July 2016
Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation Freeman, Gordon J.; Long, Andrew J.; Iwai, Yoshiko Journal of Experimental Medicine, Vol. 192, Issue 7 https://doi.org/10.1084/jem.192.7.1027	journal	October 2000
The PD-1 pathway in tolerance and autoimmunity: PD-1 pathway, Tregs, and autoimmune diseases Francisco, Loise M.; Sage, Peter T.; Sharpe, Arlene H. Immunological Reviews, Vol. 236, Issue 1 https://doi.org/10.1111/j.1600-065X.2010.00923.x	journal	June 2010
Discovering High-Affinity Ligands for Proteins: SAR by NMR Shuker, S. B.; Hajduk, P. J.; Meadows, R. P. Science, Vol. 274, Issue 5292, p. 1531-1534 https://doi.org/10.1126/science.274.5292.1531	journal	November 1996
Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors Patnaik, Amita; Kang, S. Peter; Rasco, Drew Clinical Cancer Research, Vol. 21, Issue 19 https://doi.org/10.1158/1078-0432.CCR-14-2607	journal	May 2015
Immune surveillance of tumors Swann, Jeremy B.; Smyth, Mark J. Journal of Clinical Investigation, Vol. 117, Issue 5 https://doi.org/10.1172/JCI31405	journal	May 2007
The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors Lee, Carol M.; Tannock, Ian F. BMC Cancer, Vol. 10, Issue 1 https://doi.org/10.1186/1471-2407-10-255	journal	June 2010
Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations Gong, Jun; Chehrazi-Raffle, Alexander; Reddi, Srikanth Journal for ImmunoTherapy of Cancer, Vol. 6, Issue 1 https://doi.org/10.1186/s40425-018-0316-z	journal	January 2018
Phase I Study of Single-Agent Anti–Programmed Death-1 (MDX-1106) in Refractory Solid Tumors: Safety, Clinical Activity, Pharmacodynamics, and Immunologic Correlates Brahmer, Julie R.; Drake, Charles G.; Wollner, Ira Journal of Clinical Oncology, Vol. 28, Issue 19 https://doi.org/10.1200/JCO.2009.26.7609	journal	July 2010
Cancer immunotherapies, their safety and toxicity Alatrash, Gheath; Jakher, Haroon; Stafford, Patricia D. Expert Opinion on Drug Safety, Vol. 12, Issue 5 https://doi.org/10.1517/14740338.2013.795944	journal	May 2013
Small-molecule inhibitors of PD-1/PD-L1 immune checkpoint alleviate the PD-L1-induced exhaustion of T-cells Skalniak, Lukasz; Zak, Krzysztof M.; Guzik, Katarzyna Oncotarget, Vol. 8, Issue 42 https://doi.org/10.18632/oncotarget.20050	journal	August 2017
Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1) Zak, Krzysztof M.; Grudnik, Przemyslaw; Guzik, Katarzyna Oncotarget, Vol. 7, Issue 21 https://doi.org/10.18632/oncotarget.8730	journal	April 2016
Current Diagnosis and Management of Immune Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitor Therapy Kumar, Vivek; Chaudhary, Neha; Garg, Mohit Frontiers in Pharmacology, Vol. 8 https://doi.org/10.3389/fphar.2017.00049	journal	February 2017

Cited By (7)

Comprehensive in vitro characterization of PD-L1 small molecule inhibitors Ganesan, Aravindhan; Ahmed, Marawan; Okoye, Isobel Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-48826-6	journal	August 2019
Computational Insight Into the Small Molecule Intervening PD-L1 Dimerization and the Potential Structure-Activity Relationship Shi, Danfeng; An, Xiaoli; Bai, Qifeng Frontiers in Chemistry, Vol. 7 https://doi.org/10.3389/fchem.2019.00764	journal	November 2019
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 Molecules, Vol. 24, Issue 11 https://doi.org/10.3390/molecules24112071	journal	May 2019
Comprehensive in vitro characterization of PD-L1 small molecule inhibitors Ganesan, Aravindhan; Ahmed, Marawan; Okoye, Isobel Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-48826-6	journal	August 2019
Structural insights and binding analysis for determining the molecular bases for programmed cell death protein ligand-1 inhibition Acúrcio, Rita C.; Leonardo-Sousa, Carlota; García-Sosa, Alfonso T. MedChemComm, Vol. 10, Issue 10 https://doi.org/10.1039/c9md00326f	journal	January 2019
The Characteristics of PD-L1 Inhibitors, from Peptides to Small Molecules Zhong, Yanwen; Li, Xuanyi; Yao, Hequan Molecules, Vol. 24, Issue 10 https://doi.org/10.3390/molecules24101940	journal	May 2019
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 Molecules, Vol. 24, Issue 11 https://doi.org/10.3390/molecules24112071	journal	May 2019

Similar Records

Far upstream element-binding protein 1 is up-regulated in pancreatic cancer and modulates immune response by increasing programmed death ligand 1

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23107773

Fan, Ping; Ma, Jinlong; Jin, Xin

Frequencies and expression levels of programmed death ligand 1 (PD-L1) in circulating tumor RNA (ctRNA) in various cancer types

Journal Article · 2018 · Biochemical and Biophysical Research Communications · OSTI ID:23125164

Ishiba, Toshiyuki; Hoffmann, Andreas-Claudius; Usher, Joshua; +3 more

Programmed death-1 receptor (PD-1) and PD-ligand-1 (PD-L1) expression in non-small cell lung cancer and the immune-suppressive effect of anaerobic glycolysis

Journal Article · 2019 · Medical Oncology (Online) · OSTI ID:22938388

Giatromanolaki, Alexandra; Koukourakis, Ioannis M.; Balaska, Konstantina; +2 more

Related Subjects

60 APPLIED LIFE SCIENCES
Cancer drug discovery
Fragment-based screening
Immunotherapy
PD-L1 inhibitor
Structure-based design

Title: Fragment-based screening of programmed death ligand 1 (PD-L1)

Citation Formats

References (29)

Cited By (7)

Similar Records

Related Subjects