About: N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice

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About: N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice
Creator	Bhagat, Hiral Brenman, Jay Compton, Sarah Forsbergid, Lawrence Jackson, Kimberly Laudeman, Christopher Musso, David Nierobisz, Lidia Sextonid, Jonathan Yiid, Na
source	PMC
abstract	Obesity and insulin resistance are primary risk factors for Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD is generally exhibited by non-progressive simple steatosis. However, a significant subset of patient’s progress to nonalcoholic steatohepatitis (NASH) that is defined by the presence of steatosis, inflammation and hepatocyte injury with fibrosis. Unfortunately, there are no approved therapies for NAFLD or NASH and therefore therapeutic approaches are urgently needed. Niclosamide is an U.S. Food and Drug Administration (FDA)-approved anthelmintic drug that mediates its effect by uncoupling oxidative phosphorylation. Niclosamide and its salt forms, Niclosamide Ethanolamine (NEN), and Niclosamide Piperazine (NPP) have shown efficacy in murine models of diet induced obesity characterized by attenuation of the prominent fatty liver disease phenotype and improved glucose metabolism. While the exact mechanism(s) underlying these changes remains unclear, the ability to uncouple oxidative phosphorylation leading to increased energy expenditure and lipid metabolism or attenuation of PKA mediated glucagon signaling in the liver have been proposed. Unfortunately, niclosamide has very poor water solubility, leading to low oral bioavailability. This, in addition to mitochondrial uncoupling activity and potential genotoxicity have reduced enthusiasm for its clinical use. More recently, salt forms of niclosamide, NEN and NPP, have demonstrated improved oral bioavailability while retaining activity. This suggests that development of safer more effective niclosamide derivatives for the treatment of NAFLD and Type 2 Diabetes may be possible. Herein we explored the ability of a series of N-substituted phenylbenzamide derivatives of the niclosamide salicylanilide chemotype to attenuate hepatic steatosis using a novel phenotypic in vitro model of fatty liver and the high fat diet-fed mouse model of diet induced obesity. These studies identified novel compounds with improved pre-clinical properties that attenuate hepatic steatosis in vitro and in vivo. These compounds with improved drug properties may be useful in alleviating symptoms and protection against disease progression in patients with metabolic syndrome and NAFLD.
has issue date	2018-10-25(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0204605
bibo:pmid	30359371
has license	cc-by
sha1sum (hex)	710d63d02151ad5a6ed5eb93dd30d7a531445402
schema:url	https://doi.org/10.1371/journal.pone.0204605
resource representing a document's title	N-substituted phenylbenzamides of the niclosamide chemotype attenuate obesity related changes in high fat diet fed mice
has PubMed Central identifier	PMC6201879
has PubMed identifier	30359371
schema:publication	PLoS One
resource representing a document's body	covid:710d63d02151ad5a6ed5eb93dd30d7a531445402#body_text
is schema:about of	named entity 'ABILITY TO' named entity 'HIGH FAT DIET' named entity 'RELATED' named entity 'OBESITY' named entity 'DRUG' named entity 'RETAINING' named entity 'ORG' named entity 'IMPROVED' named entity 'PRESENCE OF' named entity 'JACKSON' named entity 'NICLOSAMIDE' named entity 'ORAL BIOAVAILABILITY' named entity 'INCREASED ENERGY EXPENDITURE' named entity 'UNCLEAR' named entity 'EFFICACY' named entity 'APPROVED' named entity 'MEDIATED' named entity 'SIGNALING' named entity 'VERY POOR' named entity 'UNDERLYING' named entity 'USING' named entity 'CHARACTERIZED' named entity 'ATTENUATE' named entity 'IN VIVO' named entity 'RELATED' named entity 'NPP' named entity 'DEFINED' named entity 'DEMONSTRATED' named entity 'NON-PROGRESSIVE' named entity 'ETHANOLAMINE' named entity 'SERIES' named entity 'KMP' named entity 'PONE' named entity 'PRE-CLINICAL' named entity 'FORMS' named entity 'NEEDED' named entity 'USE' named entity 'SUBSET' named entity 'NOVEL' named entity 'INJURY' named entity 'FATTY LIVER DISEASE' named entity 'UNCOUPLING' named entity 'OCTOBER' named entity 'LIVER' named entity 'DIET' named entity 'PROPERTIES' named entity 'CHEMOTYPE' named entity 'EFFECT' named entity 'THERAPEUTIC' named entity 'GENOTOXICITY' named entity 'MICE' named entity 'PATIENT' named entity 'IN VITRO' named entity 'DISEASE PHENOTYPE' named entity 'PROPOSED' named entity '2F10' named entity 'OPEN' named entity 'DEVELOPMENT' named entity 'LOW' named entity 'RECENTLY' named entity 'IDENTIFIED' named entity 'APPROACHES' named entity 'NAFLD' named entity '27S' named entity 'ANTHELMINTIC' named entity 'SALT' named entity 'OBESITY' named entity 'SALICYLANILIDE' named entity 'HAVE' named entity 'HTTPS' named entity 'GLUCOSE METABOLISM' named entity 'MECHANISM'

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