Sepsis is a debilitating clinical syndrome of systemic inflammation in response to microorganisms especially Gram-positive and Gram-negative bacteria. A minority of sepsis cases could be due to non-pathogenic insult such as trauma. Much of the tissue and organ injury observed among septic patients is a consequence of the inflammatory response. The search for effective treatments of sepsis has led to several studies by different research groups across the globe. Although many targets and molecules have been identified, there is still no effective treatment for sepsis. The aim of this report is to review the literature on drugs and drug candidates against sepsis and how they modulate the expression of inflammatory genes. Many compounds have been identified to regulate inflammatory gene expression by interacting with targets such as topoisomerase 1 and nuclear factor kappa B, which regulate the production of pro- and anti-inflammatory cytokines. Even though these compounds appear promising as potential drugs against sepsis, no effective therapies have been discovered to date and thus the fight against sepsis continues.
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http://dx.doi.org/10.2174/1570163815666180227162926 | DOI Listing |
J Chem Inf Model
January 2025
Department of Computer Science and Technology, Shantou University, Shantou 515063, China.
The human microbiota may influence the effectiveness of drug therapy by activating or inactivating the pharmacological properties of drugs. Computational methods have demonstrated their ability to screen reliable microbe-drug associations and uncover the mechanism by which drugs exert their functions. However, the previous prediction methods failed to completely exploit the neighborhood topologies of the microbe and drug entities and the diverse correlations between the microbe-drug entity pair and the other entities.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Neurology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
The death signaling complex comprising extrasynaptic NMDAR and TRPM4 plays a pivotal role in the pathogenesis of ischemic stroke. Targeting the protein-protein interactions between NMDAR and TRPM4 represents a promising therapeutic strategy for ischemic stroke. Herein, we describe the discovery of a novel series of NMDAR/TRPM4 interaction interface inhibitors aimed at enhancing neuroprotective efficacy and optimizing pharmacokinetic profiles.
View Article and Find Full Text PDFAppl Environ Microbiol
December 2024
Department of Gastrocolorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin, China.
In confronting the significant challenge posed by multidrug-resistant (MDR) pathogens, particularly methicillin-resistant (MRSA), the development of innovative anti-infective strategies is essential. Our research focuses on sortase A (SrtA), a vital enzyme for anchoring surface proteins in . We discovered that plantamajoside (PMS), a phenylpropanoid glycoside extracted from .
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, Ciudad Universitaria s/n, Madrid, Community of Madrid, Spain.
Drug development for congenital toxoplasmosis is challenging since first-line therapy has a high rate of adverse effects and exhibits suboptimal efficacy. Bumped kinase inhibitors (BKIs), targeting protein kinases with small gatekeeper residues, have been found to be effective against . The efficacy of BKI-1748 administered later than 2 days post-infection (p.
View Article and Find Full Text PDFACS Chem Neurosci
January 2025
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, United States.
Receptor interacting protein kinase 1 (RIPK1) crucially upregulates necroptosis and is a key driver of inflammation. An effective PET radioligand for imaging brain RIPK1 would be useful for further exploring the role of this enzyme in neuroinflammation and for assisting drug discovery. Here, we report our progress on developing a PET radioligand for RIPK1 based on the phenyl-1-dihydropyrazole skeleton of a lead RIPK1 inhibitor, GSK'963.
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