BoNT Inhibitors
| type A type B type F BoNT Inhibitor Resources |
BoNT Inhibitors
Binding, translocation and protease inhibitors composed
of peptides and small molecules are being identified and
developed to neutralize BoNT toxins.
Botulinum toxin is transported by epithelial cells to
target cells in the peripheral cholinergic nerve endings. This
process involves a series of steps in which the toxin binds to neuronal receptors,
undergoes receptor-mediated endocytosis and endosomal membrane
translocation. Lastly, the toxin's endoprotease light chain inactivates neuronal proteins,
thereby blocking neurotransmitter release.
Inhibitor affinity is quantified by the equilibrium
dissociation constant, Ki. The Ki value is the
concentration of the inhibitor at which 50% inhibition
occurs, hence the receptors affinity for
the inhibitor is high when the Ki is low.
Serotype |
Inhibitor Name |
Affinity (Ki value) |
PubMed ID |
Inhibition Type or Synthetic Peptides |
| type A | BoNT/A LC inhibitor, 1 | 18 ± 2 µM | PMID: 16855686 | Metalloprotease inhibitor, non-peptidic (small molecule); Efficacy in a cell-based assay |
| michellamine B | 20 µM (60% inhibition) | PMID: 14511652 | Metalloprotease inhibitor non-peptidic (small molecule) | |
| N-acetyl-2-mercapto-3-phenyl propionly-RATKML-amide | 0.33 µM (4B) 8 µM (4A) | PMID: 12482605 | Metalloprotease inhibitor, N-terminus is an analog of phenylalanine | |
| N-acetyl-cysteine-RATKML-amide | 2 µM | PMID: 12482605 | Metalloprotease inhibitor | |
| N-acetyl-2-mercapto propionyl-RATKML-amide | 1 µM (3A) 30 µM (3B) | PMID: 12482605 | Metalloprotease inhibitor, N-terminus is an analog of alanine | |
| N-acetyl-2-methyl-3-mercapto propionyl-RATKML-amide | 20 µM (1B) 50 µM (1A) | PMID: 12482605 | Metalloprotease inhibitor Analog of captopril, ACE inhibitor | |
| Q2-15 | 20 µM (60% inhibition) | PMID: 14511652 | Metalloprotease inhibitor, non-peptidic (small molecule) | |
| type B | BABIM | 5-10 µM | PMID: 9662424 | Metalloprotease inhibitor |
| Biphenyl/benzo-thienyl methyl derivative | 0.02 µM | PMID: 12146945 | Metalloprotease inhibitor | |
| Bis-derivative | 2.3 nM | PMID: 14561084 | Metalloprotease inhibitor | |
| ICD-1578 | 27µM | PMID: 9662424 | Metalloprotease inhibitor | |
| type F | peptide 42-58/Q58D-C | 9 µM | PMID: 15751983 | Synthetic Peptide |
| peptide 37-58/Q58D-C | 0.28 µM | PMID: 15751983 | Synthetic Peptide | |
| peptide 32-58/Q58D-C | 0.034 µM | PMID: 15751983 | Synthetic Peptide | |
| peptide 27-58/Q58D-C | 1.9 nM | PMID: 15751983 | Synthetic Peptide | |
| peptide 22-58/Q58D-C | 1.0 nM | PMID: 15751983 | Synthetic Peptide | |
| peptide 17-58/Q58D-C | 1.3 nM | PMID: 15751983 | Synthetic Peptide |
BoNT Inhibitor Resources
BoNT/A Inhibitors
- BoNT/A LC Inhibitors in Burnett et al. 2005 Nature
Reviews
(Table 5)
- BoNT/A LC Inhibitors in Burnett et al. 2005 Nature
Reviews
BoNT/B Inhibitors
- bis(5-amidino-2-benzimidazolyl)methane (BABIM)
at Brookhaven National Laboratory
- BoNT/B LC Inhibitors in Burnett et al. 2005 Nature
Reviews
(Table 6)
- bis(5-amidino-2-benzimidazolyl)methane (BABIM)
at Brookhaven National Laboratory
BotDB A Database Resource for the Clostridial Neurotoxins
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