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Updated: Mar 13, 2026

A High-throughput-compatible FRET-based Platform for Identification and Characterization of Botulinum Neurotoxin Light Chain Modulators
Published on: December 27, 2013
Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain
Paul T Bremer1, Song Xue1, Kim D Janda1
1Departments of Chemistry, Immunology and Microbial Sciences, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. kdjanda@scripps.edu.
Abstract:
In developing small-molecule inhibitors of botulinum neurotoxin serotype A light chain (BoNT/A LC), substituted picolinic acids were identified. Extensive investigation into the SAR of the picolinic acid scaffold revealed 5-(1-butyl-4-chloro-1H-indol-2-yl)picolinic acid (CBIP), which possessed low micromolar activity against BoNT/A. Kinetic and docking studies demonstrated binding of CBIP to the β-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.
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