Enantiospecific effects of ketoconazole on aryl hydrocarbon receptor

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F14%3A33150560" target="_blank" >RIV/61989592:15310/14:33150560 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15110/14:33150560

Result on the web

<a href="http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0101832" target="_blank" >http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0101832</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0101832" target="_blank" >10.1371/journal.pone.0101832</a>

Result language

angličtina

Original language name

Enantiospecific effects of ketoconazole on aryl hydrocarbon receptor

Original language description

Azole antifungal ketoconazole (KET) was demonstrated to activate aryl hydrocarbon receptor (AhR). Since clinically used KET is a racemic mixture of two cis-enantiomers (2R,4S)-(+)-KET and (2S,4R)-(-)-KET,we examined the effects of KET enantiomers on AhRsignaling pathway. (+)-KET dose-dependently activated AhR in human gene reporter cell line AZ-AHR,and displayed 5-20x higher agonist activity (efficacy),as compared to (-)-KET; both enantiomers were AhR antagonists with equal potency (IC50). Consistently,(+)-KET strongly induced CYP1A1 mRNA and protein in human HepG2 cells,while (-)-KET exerted less than 10% of (+)-KET activity. In primary human hepatocytes,both enantiomers preferentially induced CYP1A2 over CYP1A1 mRNA and protein,and the potency of (+)-KET was slightly higher as compared to (-)-KET. Ligand binding assay with guinea pig liver cytosols revealed that both (+)-KET and (-)-KET are weak ligands of AhR that displaced [H-3]-TCDD with comparable potency. Similarly,both enantio

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

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Project

<a href="/en/project/GA13-01809S" target="_blank" >GA13-01809S: Enantiospecific interactions between clinically used chiral drugs and regulatory pathways of human cytochromes P450.</a><br>

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

PLoS One

ISSN

1932-6203

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

12

Pages from-to

"e101832"

UT code for WoS article

000338637300092

EID of the result in the Scopus database

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