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Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication
Microbiotix, Inc., One Innovation Drive, Worcester, MA 01605, USA
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; in revised form: 20 December 2010 / Accepted: 29 December 2010 / Published: 30 December 2010
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
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Cite This Article
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.
Li B, Peet NP, Butler MM, Burnett JC, Moir DT, Bowlin TL. Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication. Molecules. 2011; 16(1):202-220.
Li, Bing; Peet, Norton P.; Butler, Michelle M.; Burnett, James C.; Moir, Donald T.; Bowlin, Terry L. 2011. "Small Molecule Inhibitors as Countermeasures for Botulinum Neurotoxin Intoxication." Molecules 16, no. 1: 202-220.