Matches in SemOpenAlex for { <https://semopenalex.org/work/W2093804516> ?p ?o ?g. }
Showing items 1 to 98 of
98
with 100 items per page.
- W2093804516 endingPage "293" @default.
- W2093804516 startingPage "288" @default.
- W2093804516 abstract "Botulinum neurotoxin (BoNT), the etiological agent that causes the neuroparalytic disease botulism, has become a highly studied drug target in light of the potential abuse of this toxin as a weapon of bioterrorism. In particular, small molecule inhibitors of the light chain metalloprotease of BoNT serotype A have received significant attention and a number of small molecule and biologic inhibitors have been reported. However, all small molecules reported have been identified from either primary screens or medicinal chemistry follow-up studies, and the pharmacokinetic profiles of these compounds have not been addressed. In this study, we have removed the pharmacologic liabilities of one of the best compounds reported to date, 2,4-dichlorocinnamate hydroxamic acid, and in the process uncovered a related class of benzothiophene hydroxamic acids that are significantly more potent inhibitors of the BoNT/A light chain, while also possessing greatly improved ADME properties, with the best compound showing the most potent inhibition of BoNT/A light chain reported (Ki = 77 nM). Using a strategy of incorporating traditional drug development filters early into the discovery process, potential liabilities in BoNT/A lead compounds have been illuminated and removed, clearing the path for advancement into further pharmacologic optimization and in vivo efficacy testing." @default.
- W2093804516 created "2016-06-24" @default.
- W2093804516 creator A5000505037 @default.
- W2093804516 creator A5030107136 @default.
- W2093804516 creator A5033744726 @default.
- W2093804516 creator A5063909726 @default.
- W2093804516 creator A5074363486 @default.
- W2093804516 creator A5086664284 @default.
- W2093804516 date "2011-04-12" @default.
- W2093804516 modified "2023-10-17" @default.
- W2093804516 title "Enhancing the Pharmacokinetic Properties of Botulinum Neurotoxin Serotype A Protease Inhibitors through Rational Design" @default.
- W2093804516 cites W1918147071 @default.
- W2093804516 cites W1969766259 @default.
- W2093804516 cites W1970220792 @default.
- W2093804516 cites W1982131915 @default.
- W2093804516 cites W2005531630 @default.
- W2093804516 cites W2006490581 @default.
- W2093804516 cites W2014688619 @default.
- W2093804516 cites W2030808052 @default.
- W2093804516 cites W2036058992 @default.
- W2093804516 cites W2040721469 @default.
- W2093804516 cites W2048654645 @default.
- W2093804516 cites W2055846812 @default.
- W2093804516 cites W2077888217 @default.
- W2093804516 cites W2081769761 @default.
- W2093804516 cites W2083354933 @default.
- W2093804516 cites W2114556103 @default.
- W2093804516 cites W2119305815 @default.
- W2093804516 cites W2122977798 @default.
- W2093804516 cites W2128931040 @default.
- W2093804516 cites W2133193987 @default.
- W2093804516 cites W2137889830 @default.
- W2093804516 doi "https://doi.org/10.1021/cn200021q" @default.
- W2093804516 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3129992" @default.
- W2093804516 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21743830" @default.
- W2093804516 hasPublicationYear "2011" @default.
- W2093804516 type Work @default.
- W2093804516 sameAs 2093804516 @default.
- W2093804516 citedByCount "19" @default.
- W2093804516 countsByYear W20938045162012 @default.
- W2093804516 countsByYear W20938045162013 @default.
- W2093804516 countsByYear W20938045162014 @default.
- W2093804516 countsByYear W20938045162015 @default.
- W2093804516 countsByYear W20938045162016 @default.
- W2093804516 countsByYear W20938045162017 @default.
- W2093804516 countsByYear W20938045162018 @default.
- W2093804516 countsByYear W20938045162020 @default.
- W2093804516 countsByYear W20938045162022 @default.
- W2093804516 crossrefType "journal-article" @default.
- W2093804516 hasAuthorship W2093804516A5000505037 @default.
- W2093804516 hasAuthorship W2093804516A5030107136 @default.
- W2093804516 hasAuthorship W2093804516A5033744726 @default.
- W2093804516 hasAuthorship W2093804516A5063909726 @default.
- W2093804516 hasAuthorship W2093804516A5074363486 @default.
- W2093804516 hasAuthorship W2093804516A5086664284 @default.
- W2093804516 hasBestOaLocation W20938045162 @default.
- W2093804516 hasConcept C112705442 @default.
- W2093804516 hasConcept C161624437 @default.
- W2093804516 hasConcept C185592680 @default.
- W2093804516 hasConcept C2780035454 @default.
- W2093804516 hasConcept C55493867 @default.
- W2093804516 hasConcept C69366308 @default.
- W2093804516 hasConcept C71924100 @default.
- W2093804516 hasConcept C74187038 @default.
- W2093804516 hasConcept C98274493 @default.
- W2093804516 hasConceptScore W2093804516C112705442 @default.
- W2093804516 hasConceptScore W2093804516C161624437 @default.
- W2093804516 hasConceptScore W2093804516C185592680 @default.
- W2093804516 hasConceptScore W2093804516C2780035454 @default.
- W2093804516 hasConceptScore W2093804516C55493867 @default.
- W2093804516 hasConceptScore W2093804516C69366308 @default.
- W2093804516 hasConceptScore W2093804516C71924100 @default.
- W2093804516 hasConceptScore W2093804516C74187038 @default.
- W2093804516 hasConceptScore W2093804516C98274493 @default.
- W2093804516 hasIssue "6" @default.
- W2093804516 hasLocation W20938045161 @default.
- W2093804516 hasLocation W20938045162 @default.
- W2093804516 hasLocation W20938045163 @default.
- W2093804516 hasLocation W20938045164 @default.
- W2093804516 hasOpenAccess W2093804516 @default.
- W2093804516 hasPrimaryLocation W20938045161 @default.
- W2093804516 hasRelatedWork W1972857466 @default.
- W2093804516 hasRelatedWork W1987184004 @default.
- W2093804516 hasRelatedWork W2088837113 @default.
- W2093804516 hasRelatedWork W2156868660 @default.
- W2093804516 hasRelatedWork W2169495846 @default.
- W2093804516 hasRelatedWork W3095243115 @default.
- W2093804516 hasRelatedWork W4220992614 @default.
- W2093804516 hasRelatedWork W4231915261 @default.
- W2093804516 hasRelatedWork W4238064147 @default.
- W2093804516 hasRelatedWork W942515233 @default.
- W2093804516 hasVolume "2" @default.
- W2093804516 isParatext "false" @default.
- W2093804516 isRetracted "false" @default.
- W2093804516 magId "2093804516" @default.
- W2093804516 workType "article" @default.