Molecules 2011, 16(1), 202-220; doi:10.3390/molecules16010202
Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication
1
Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA
2
Target, Structure-Based Drug Discovery Group, SAIC-Frederick, Inc., National Cancer Institute at Frederick, 1050 Boyles Street, Frederick, MD 21702, USA
*
Author to whom correspondence should be addressed.
Received: 30 November 2010 / Revised: 20 December 2010 / Accepted: 29 December 2010 / Published: 30 December 2010
(This article belongs to the Special Issue Toxins - Organic and Analytical Chemistry)
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Abstract
Botulinum neurotoxins (BoNTs) are the most potent of known toxins and are listed as category A biothreat agents by the U.S. CDC. The BoNT-mediated proteolysis of SNARE proteins inhibits the exocytosis of acetylcholine into neuromuscular junctions, leading to life-threatening flaccid paralysis. Currently, the only therapy for BoNT intoxication (which results in the disease state botulism) includes experimental preventative antibodies and long-term supportive care. Therefore, there is an urgent need to identify and develop inhibitors that will serve as both prophylactic agents and post-exposure ‘rescue’ therapeutics. This review focuses on recent progress to discover and develop small molecule inhibitors as therapeutic countermeasures for BoNT intoxication.Keywords:
inum neurotoxin; inhibitor; drug discovery
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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MDPI and ACS Style
Li, B.; Peet, N.P.; Butler, M.M.; Burnett, J.C.; Moir, D.T.; Bowlin, T.L. Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication. Molecules 2011, 16, 202-220.
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