Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Standard

Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. / Gessier, Francois; Preuss, Inga; Yin, Hong; Rosenkilde, Mette Marie; Laurent, Stephane; Endres, Ralf; Chen, Yu A; Marsilje, Thomas H; Seuwen, Klaus; Nguyen, Deborah G; Sailer, Andreas W.

I: Journal of Medicinal Chemistry, Bind 57, Nr. 8, 24.04.2014, s. 3358-68.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Gessier, F, Preuss, I, Yin, H, Rosenkilde, MM, Laurent, S, Endres, R, Chen, YA, Marsilje, TH, Seuwen, K, Nguyen, DG & Sailer, AW 2014, 'Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor', Journal of Medicinal Chemistry, bind 57, nr. 8, s. 3358-68. https://doi.org/10.1021/jm4019355

APA

Gessier, F., Preuss, I., Yin, H., Rosenkilde, M. M., Laurent, S., Endres, R., Chen, Y. A., Marsilje, T. H., Seuwen, K., Nguyen, D. G., & Sailer, A. W. (2014). Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. Journal of Medicinal Chemistry, 57(8), 3358-68. https://doi.org/10.1021/jm4019355

Vancouver

Gessier F, Preuss I, Yin H, Rosenkilde MM, Laurent S, Endres R o.a. Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. Journal of Medicinal Chemistry. 2014 apr. 24;57(8):3358-68. https://doi.org/10.1021/jm4019355

Author

Gessier, Francois ; Preuss, Inga ; Yin, Hong ; Rosenkilde, Mette Marie ; Laurent, Stephane ; Endres, Ralf ; Chen, Yu A ; Marsilje, Thomas H ; Seuwen, Klaus ; Nguyen, Deborah G ; Sailer, Andreas W. / Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor. I: Journal of Medicinal Chemistry. 2014 ; Bind 57, Nr. 8. s. 3358-68.

Bibtex

@article{7d1c175e56224e23b8d030d82a3f8695,
title = "Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor",
abstract = "Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) ( Nature 2011 , 475 , 524 ; 519 ). EBI2 is highly expressed in immune cells ( J. Biol. Chem. 2006 , 281 , 13199 ), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes ( Nature 2010 , 467 , 460 ). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.",
keywords = "Animals, CHO Cells, Calcium, Cricetulus, Herpesvirus 4, Human, Humans, Male, Mice, Mice, Inbred C57BL, Receptors, G-Protein-Coupled, U937 Cells",
author = "Francois Gessier and Inga Preuss and Hong Yin and Rosenkilde, {Mette Marie} and Stephane Laurent and Ralf Endres and Chen, {Yu A} and Marsilje, {Thomas H} and Klaus Seuwen and Nguyen, {Deborah G} and Sailer, {Andreas W}",
year = "2014",
month = apr,
day = "24",
doi = "10.1021/jm4019355",
language = "English",
volume = "57",
pages = "3358--68",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "8",

}

RIS

TY - JOUR

T1 - Identification and characterization of small molecule modulators of the Epstein-Barr virus-induced gene 2 (EBI2) receptor

AU - Gessier, Francois

AU - Preuss, Inga

AU - Yin, Hong

AU - Rosenkilde, Mette Marie

AU - Laurent, Stephane

AU - Endres, Ralf

AU - Chen, Yu A

AU - Marsilje, Thomas H

AU - Seuwen, Klaus

AU - Nguyen, Deborah G

AU - Sailer, Andreas W

PY - 2014/4/24

Y1 - 2014/4/24

N2 - Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) ( Nature 2011 , 475 , 524 ; 519 ). EBI2 is highly expressed in immune cells ( J. Biol. Chem. 2006 , 281 , 13199 ), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes ( Nature 2010 , 467 , 460 ). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.

AB - Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) ( Nature 2011 , 475 , 524 ; 519 ). EBI2 is highly expressed in immune cells ( J. Biol. Chem. 2006 , 281 , 13199 ), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes ( Nature 2010 , 467 , 460 ). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.

KW - Animals

KW - CHO Cells

KW - Calcium

KW - Cricetulus

KW - Herpesvirus 4, Human

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Receptors, G-Protein-Coupled

KW - U937 Cells

U2 - 10.1021/jm4019355

DO - 10.1021/jm4019355

M3 - Journal article

C2 - 24678947

VL - 57

SP - 3358

EP - 3368

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 8

ER -

ID: 137818108