ArticleDrug design, development and therapy2017
MC-PPEA as a new and more potent inhibitor of CLP-induced sepsis and pulmonary inflammation than FK866.
Article in Drug design, development and therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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
5 citing papers in PubMed, 11 citations in OpenAlex.
- The Role of Adipose Tissue and Adipokines in Sepsis: Inflammatory and Metabolic Considerations, and the Obesity Paradox.Current obesity reports · 2019Review
- Essential Role of Visfatin in Lipopolysaccharide and Colon Ascendens Stent Peritonitis-Induced Acute Lung Injury.International journal of molecular sciences · 2019Article
- Epigenetic regulation of NfatC1 transcription and osteoclastogenesis by nicotinamide phosphoribosyl transferase in the pathogenesis of arthritis.Cell death discovery · 2019Article
- Clickable prodrugs bearing potent and hydrolytically cleavable nicotinamide phosphoribosyltransferase inhibitors.Drug design, development and therapy · 2018Article
- Epigenetic regulation of Runx2 transcription and osteoblast differentiation by nicotinamide phosphoribosyltransferase.Cell & bioscience · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study indicated that overexpression of nicotinamide phosphoribosyltransferase (NAMPT) aggravated acute lung injury, while knockdown of NAMPT expression attenuated ventilator-induced lung injury. Recently, we found that meta-carborane-butyl-3-(3-pyridinyl)-2E-propenamide (MC-PPEA, MC4), in which the benzoylpiperidine moiety of FK866 has been replaced by a carborane, displayed a 100-fold increase in NAMPT inhibition over FK866. Here, we determined the effects of MC4 and FK866 on cecal ligation and puncture (CLP) surgery-induced sepsis in C57BL/6J mice. MC4 showed stronger inhibitory effects than FK866 on CLP-induced mortality, serum tumor necrosis factor α (TNFα) levels, pulmonary myeloperoxidase activity, alveolar injury, and interleukin 6 and interleukin1β messenger RNA levels. In vitro cell permeability and electric cell-substrate impedance sensing assays demonstrated that MC4 inhibited TNFα- and thrombin-mediated pulmonary endothelial cell permeability better than FK866. MC4 also exerted more potent effects than FK866, at concentrations as low as 0.3 nM, to attenuate TNFα-mediated intracellular cytokine expression, nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH levels, and nuclear factor kappa B p65 phosphorylation and nuclear translocation in A549 cells. Our results strongly suggest that the newly developed MC4 is a more potent suppressor of CLP-induced pulmonary inflammation and sepsis than FK866, with potential clinical application as a new treatment agent for sepsis and inflammation.
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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.