Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists

Matthew D. Morin, Ying Wang, Brian T. Jones, Lijing Su, Murali M R P Surakattula, Michael Berger, Hua Huang, Elliot K. Beutler, Hong Zhang, Bruce Beutler, Dale L. Boger

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

Original languageEnglish (US)
Pages (from-to)4812-4830
Number of pages19
JournalJournal of Medicinal Chemistry
Volume59
Issue number10
DOIs
StatePublished - May 26 2016

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Morin, M. D., Wang, Y., Jones, B. T., Su, L., Surakattula, M. M. R. P., Berger, M., Huang, H., Beutler, E. K., Zhang, H., Beutler, B., & Boger, D. L. (2016). Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists. Journal of Medicinal Chemistry, 59(10), 4812-4830. https://doi.org/10.1021/acs.jmedchem.6b00177