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Chemrxiv

Structure-activity relationship studies of Retro-1 analogues against Shiga toxin

Abdelkafi, H;Michau, A;Pons, V;Ngadjeua, F;Clerget, A;Ouarab, LA;Buisson, D;Caramelle, L;Gillet, D;Barbier, J;Cintrat, J;

The Retro-1 molecule was identified in a high-throughput screening as an inhibitor of ricin and Shiga toxins by diminishing their intracellular trafficking _via_ the retrograde route, from early endosomes to the Golgi apparatus. In order to improve the activity of Retro-1, a SAR study was undertaken yielding an analog that possesses roughly 70-fold better EC50 against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.

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