A series of calixarenes identified as TLR4 antagonists

A panel of amphiphilic guanidinocalixarenes has been shown to be modulators of the Toll-like receptor 4 signaling.

The computational studies performed by Sonsoles Martín-Santamaría´s group from CIB-CSIC, and recently published in the Journal of Medicinal Chemistry in a work in collaboration with the Universities of Parma and Milano-Bicocca, have supported this novel mechanism.

The authors have suggested a direct antagonist effect of calixarenes on TLR4/MD-2 dimerization, pointing at the calixarene moiety as a potential scaffold for the development of new TLR4-directed therapeutics.

Additionally, this work has been selected as cover of the journal number published on June 22nd 2017 under the explanation: “Innate immunity receptor TLR4/MD-2 “attacked” by LPS molecules from Gram-negative bacteria. Amphiphilic guanidinocalixarenes inhibit the LPS toxic action”.

[Image credit: Journal of Medicinal Chemistry]

Reference: Amphiphilic Guanidinocalixarenes Inhibit Lipopolysaccharide (LPS)- and Lectin-Stimulated Toll-like Receptor 4 (TLR4) Signaling. Stefania E. Sestito, Fabio A. Facchini, Ilaria Morbioli, Jean-Marc Billod, Sonsoles Martin-Santamaria, Alessandro Casnati, Francesco Sansone, and Francesco Peri. J. Med. Chem. (2017). DOI: 10.1021/acs.jmedchem.7b00095