ArticleBioorganic & medicinal chemistry2007
Protection from endotoxic shock by EVK-203, a novel alkylpolyamine sequestrant of lipopolysaccharide.
Article in Bioorganic & medicinal chemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 21 citations in OpenAlex.
- Biophysical mechanisms of the neutralization of endotoxins by lipopolyamines.The open biochemistry journal · 2013Article
- The Methanol Extract of Azadirachta indica A. Juss Leaf Protects Mice Against Lethal Endotoxemia and Sepsis.Biomolecules & therapeutics · 2012Article
- Structure-activity relationships in toll-like receptor 2-agonists leading to simplified monoacyl lipopeptides.Journal of medicinal chemistry · 2011Article
- Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines.Bioorganic & medicinal chemistry letters · 2009Article
- Structure-activity relationships of lipopolysaccharide sequestration in guanylhydrazone-bearing lipopolyamines.Bioorganic & medicinal chemistry · 2009Article
- Structure-activity relationships of antimicrobial and lipoteichoic acid-sequestering properties in polyamine sulfonamides.Antimicrobial agents and chemotherapy · 2009Article
- Comparison of the immunostimulatory and proinflammatory activities of candidate Gram-positive endotoxins, lipoteichoic acid, peptidoglycan, and lipopeptides, in murine and human cells.Immunology letters · 2008Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Lipopolysaccharides (LPS) play a key role in the pathogenesis of septic shock, a major cause of mortality in the critically ill patient. The only therapeutic option aimed at limiting downstream systemic inflammatory processes by targeting lipopolysaccharide is Toraymyxin, an extracorporeal hemoperfusion device using solid phase-immobilized polymyxin B (PMB). While PMB is known to effectively sequester LPS, its severe systemic toxicity proscribes its parenteral use, and hemoperfusion may not be feasible in patients in shock. In our continuing efforts to develop small-molecule mimics which display the LPS-sequestering properties, but not the toxicity of PMB, a series of mono- and bis-substituted dialkylpolyamines were synthesized and evaluated. We show that EVK-203, an alkylpolyamine compound, specifically binds to and neutralizes the activity of LPS, and affords complete protection in a murine model of endotoxic shock. EVK-203 is without any apparent toxicity when administered to mice at multiples of therapeutic doses for several days. The specific endotoxin-sequestering property along with a very favorable therapeutic index renders this compound an ideal candidate for preclinical development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.