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Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice

Authors :
Jessica Vincent
Carolina Adura
Pu Gao
Antonio Luz
Lodoe Lama
Yasutomi Asano
Rei Okamoto
Toshihiro Imaeda
Jumpei Aida
Katherine Rothamel
Tasos Gogakos
Joshua Steinberg
Seth Reasoner
Kazuyoshi Aso
Thomas Tuschl
Dinshaw J. Patel
J. Fraser Glickman
Manuel Ascano
Source :
Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017)
Publication Year :
2017
Publisher :
Nature Portfolio, 2017.

Abstract

Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
8
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.2885ccbed5fa465f9f9e037a1d7866c1
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-017-00833-9