The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F15%3A10312781" target="_blank" >RIV/00216208:11160/15:10312781 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.mdpi.com/1424-8220/15/4/9265/htm" target="_blank" >http://www.mdpi.com/1424-8220/15/4/9265/htm</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/s150409265" target="_blank" >10.3390/s150409265</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists

Popis výsledku v původním jazyce

The constitutive androstane receptor (CAR) is a critical nuclear receptor in the gene regulation of xenobiotic and endobiotic metabolism. The LanthaScreen(TM) TR-FRET CAR coactivator assay provides a simple and reliable method to analyze the affinity ofa ligand to the human CAR ligand-binding domain (LBD) with no need to use cellular models. This in silico assay thus enables the study of direct CAR ligands and the ability to distinguish them from the indirect CAR activators that affect the receptor viathe cell signaling-dependent phosphorylation of CAR in cells. For the current paper we characterized the pharmacodynamic interactions of three known CAR inverse agonists/antagonists-PK11195, clotrimazole and androstenol-with the prototype agonist CITCO(6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dic hlorobenzyl)oxime) using the TR-FRET LanthaScreen(TM) assay. We have confirmed that all three compounds are inverse agonists of human CAR, with IC50 0.51, 0.005, and

Název v anglickém jazyce

The Use of the LanthaScreen TR-FRET CAR Coactivator Assay in the Characterization of Constitutive Androstane Receptor (CAR) Inverse Agonists

Popis výsledku anglicky

The constitutive androstane receptor (CAR) is a critical nuclear receptor in the gene regulation of xenobiotic and endobiotic metabolism. The LanthaScreen(TM) TR-FRET CAR coactivator assay provides a simple and reliable method to analyze the affinity ofa ligand to the human CAR ligand-binding domain (LBD) with no need to use cellular models. This in silico assay thus enables the study of direct CAR ligands and the ability to distinguish them from the indirect CAR activators that affect the receptor viathe cell signaling-dependent phosphorylation of CAR in cells. For the current paper we characterized the pharmacodynamic interactions of three known CAR inverse agonists/antagonists-PK11195, clotrimazole and androstenol-with the prototype agonist CITCO(6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dic hlorobenzyl)oxime) using the TR-FRET LanthaScreen(TM) assay. We have confirmed that all three compounds are inverse agonists of human CAR, with IC50 0.51, 0.005, and

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GBP303%2F12%2FG163" target="_blank" >GBP303/12/G163: Centrum interakcí potravních doplňků s léčivy a nutrigenetiky</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

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

Název periodika

Sensors

ISSN

1424-8220

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

9265-9276

Kód UT WoS článku

000354236100115

EID výsledku v databázi Scopus

2-s2.0-84928152183