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Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice

Ying Wang, Lijing Su, Matthew D. Morin, Brian T. Jones, Yuto Mifune, Hexin Shi, Kuan-wen Wang, Xiaoming Zhan, Aijie Liu, Jianhui Wang, Xiaohong Li, Miao Tang, Sara Ludwig, Sara Hildebrand, Kejin Zhou, Daniel J. Siegwart, Eva Marie Y. Moresco, Hong Zhang, Dale L. Boger, and Bruce Beutler
PNAS September 11, 2018 115 (37) E8698-E8706; published ahead of print August 27, 2018 https://doi.org/10.1073/pnas.1809232115
Ying Wang
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Lijing Su
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Matthew D. Morin
bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
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Brian T. Jones
bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
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Yuto Mifune
bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
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Hexin Shi
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Kuan-wen Wang
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Xiaoming Zhan
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Aijie Liu
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Jianhui Wang
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Xiaohong Li
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Miao Tang
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Sara Ludwig
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Sara Hildebrand
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Kejin Zhou
cSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390;dDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390
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Daniel J. Siegwart
cSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390;dDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390
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Eva Marie Y. Moresco
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Hong Zhang
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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Dale L. Boger
bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
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Bruce Beutler
aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
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  • For correspondence: bruce.beutler@utsouthwestern.edu
  1. Edited by Dennis A. Carson, University of California, San Diego, La Jolla, CA, and approved July 2, 2018 (received for review June 28, 2018)

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Article Information

vol. 115 no. 37 E8698-E8706
DOI: 
https://doi.org/10.1073/pnas.1809232115
PubMed: 
30150374

Published By: 
National Academy of Sciences
Print ISSN: 
0027-8424
Online ISSN: 
1091-6490
History: 
  • Published in issue September 11, 2018.
  • Published first August 27, 2018.

Copyright & Usage: 
© 2018 Published under the PNAS license.

Author Information

  1. Ying Wanga,
  2. Lijing Sua,
  3. Matthew D. Morinb,
  4. Brian T. Jonesb,
  5. Yuto Mifuneb,
  6. Hexin Shia,
  7. Kuan-wen Wanga,
  8. Xiaoming Zhana,
  9. Aijie Liua,
  10. Jianhui Wanga,
  11. Xiaohong Lia,
  12. Miao Tanga,
  13. Sara Ludwiga,
  14. Sara Hildebranda,
  15. Kejin Zhouc,d,
  16. Daniel J. Siegwartc,d,
  17. Eva Marie Y. Morescoa,
  18. Hong Zhanga,
  19. Dale L. Bogerb, and
  20. Bruce Beutlera,1
  1. aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390;
  2. bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037;
  3. cSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390;
  4. dDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390
  1. Edited by Dennis A. Carson, University of California, San Diego, La Jolla, CA, and approved July 2, 2018 (received for review June 28, 2018)

Footnotes

  • ↵1To whom correspondence should be addressed. Email: bruce.beutler{at}utsouthwestern.edu.
  • Author contributions: Y.W. and B.B. designed research; Y.W., L.S., H.S., K.-w.W., X.Z., A.L., J.W., X.L., M.T., S.L., S.H., K.Z., D.J.S., and H.Z. performed research; M.D.M., B.T.J., Y.M., and D.L.B. contributed new reagents/analytic tools; Y.W. and B.B. analyzed data; and Y.W., E.M.Y.M., and B.B. wrote the paper.

  • Conflict of interest statement: B.B. and D.L.B. have financial interests in Tollbridge Therapeutics, LLC, which has licensed the patent for Diprovocim.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1809232115/-/DCSupplemental.

Cited By...

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This article has been cited by the following articles in journals that are participating in Crossref Cited-by Linking.

  • Diprovocims: A New and Exceptionally Potent Class of Toll-like Receptor Agonists
    Matthew D. Morin, Ying Wang, Brian T. Jones, Yuto Mifune, Lijing Su, Hexin Shi, Eva Marie Y. Moresco, Hong Zhang, Bruce Beutler, Dale L. Boger
    Journal of the American Chemical Society 2018 140 43
  • Structure-based discovery of a specific TLR1–TLR2 small molecule agonist from the ZINC drug library database
    Zhipeng Chen, Xiaohong Cen, Junjie Yang, Xiaoshan Tang, Kai Cui, Kui Cheng
    Chemical Communications 2018 54 81

Article usage

Article usage: August 2018 to February 2019

AbstractFullPdf
Aug 2018921174131
Sep 20182613722441133
Oct 20182902502268
Nov 20181315227120
Dec 201883115575
Total 20183210633021727
Jan 201989818198
Feb 20193614742
Total 20191259228140
Total3336535301867
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Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice
Ying Wang, Lijing Su, Matthew D. Morin, Brian T. Jones, Yuto Mifune, Hexin Shi, Kuan-wen Wang, Xiaoming Zhan, Aijie Liu, Jianhui Wang, Xiaohong Li, Miao Tang, Sara Ludwig, Sara Hildebrand, Kejin Zhou, Daniel J. Siegwart, Eva Marie Y. Moresco, Hong Zhang, Dale L. Boger, Bruce Beutler
Proceedings of the National Academy of Sciences Sep 2018, 115 (37) E8698-E8706; DOI: 10.1073/pnas.1809232115

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Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice
Ying Wang, Lijing Su, Matthew D. Morin, Brian T. Jones, Yuto Mifune, Hexin Shi, Kuan-wen Wang, Xiaoming Zhan, Aijie Liu, Jianhui Wang, Xiaohong Li, Miao Tang, Sara Ludwig, Sara Hildebrand, Kejin Zhou, Daniel J. Siegwart, Eva Marie Y. Moresco, Hong Zhang, Dale L. Boger, Bruce Beutler
Proceedings of the National Academy of Sciences Sep 2018, 115 (37) E8698-E8706; DOI: 10.1073/pnas.1809232115
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