114416-77-2Relevant articles and documents
Reexamining hydroxamate inhibitors of botulinum neurotoxin serotype A: Extending towards the β-exosite
Smith, Garry R.,Caglic, Dejan,Capek, Petr,Zhang, Yan,Godbole, Sujata,Reitz, Allen B.,Dickerson, Tobin J.
supporting information; experimental part, p. 3754 - 3757 (2012/07/14)
Botulinum neurotoxins (BoNTs) are the most toxic proteins known to man, exposure to which results in flaccid paralysis. Given their extreme potency, these proteins have become studied as possible weapons of bioterrorism; however, effective treatments that function after intoxication have not progressed to the clinic. Here, we have reexamined one of the most effective inhibitors, 2,4-dichlorocinnamyl hydroxamate, in the context of the known plasticity of the BoNT/A light chain metalloprotease. Our studies have shown that modifications of this compound are tolerated and result in improved inhibitors, with the best compound having an IC50 of 0.23 μM. Given the inconsistency of structure-activity relationship trends observed across similar compounds, this data argues for caution in extrapolating across structural series.
Pharmaceutical compounds
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, (2008/06/13)
Diketopiperazines of the formula: STR1 where each of R1 to R10, which may be the same or different, is independently selected from the group consisting of hydrogen, C1 -C6 alkyl unsubstituted or substituted by o
