2. Academic Validation
  3. Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin

Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin

  • J Med Chem. 2020 Aug 13;63(15):8114-8133. doi: 10.1021/acs.jmedchem.0c00298.
Hajer Abdelkafi 1,  Aurélien Michau 2,  Valérie Pons 1,  Flora Ngadjeua 2,  Alexandra Clerget 2,  Lilia Ait Ouarab 1,  David-Alexandre Buisson 1,  David Montoir 1,  Lucie Caramelle 2,  Daniel Gillet 2,  Julien Barbier 2,  Jean-Christophe Cintrat 1
Affiliations

Affiliations

  • 1 Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SCBM, 91191 Gif-sur-Yvette, France.
  • 2 Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour la Santé (DMTS), SIMoS, 91191 Gif-sur-Yvette, France.
PMID: 32648758 DOI: 10.1021/acs.jmedchem.0c00298
Abstract

High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.

Figures