Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication
by
Bing Li 1,*, Norton P. Peet 1, Michelle M. Butler 1, James C. Burnett 2, Donald T. Moir 1 and Terry L. Bowlin 1
Bing Li 1,*, Norton P. Peet 1, Michelle M. Butler 1, James C. Burnett 2, Donald T. Moir 1 and Terry L. Bowlin 1
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.
Molecules 2011, 16(1), 202-220; https://doi.org/10.3390/molecules16010202
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)
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.
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Keywords:
inum neurotoxin; inhibitor; drug discovery
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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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