Nature Communications (May 2019)
Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression
- Lodoe Lama,
- Carolina Adura,
- Wei Xie,
- Daisuke Tomita,
- Taku Kamei,
- Vitaly Kuryavyi,
- Tasos Gogakos,
- Joshua I. Steinberg,
- Michael Miller,
- Lavoisier Ramos-Espiritu,
- Yasutomi Asano,
- Shogo Hashizume,
- Jumpei Aida,
- Toshihiro Imaeda,
- Rei Okamoto,
- Andy J. Jennings,
- Mayako Michino,
- Takanobu Kuroita,
- Andrew Stamford,
- Pu Gao,
- Peter Meinke,
- J. Fraser Glickman,
- Dinshaw J. Patel,
- Thomas Tuschl
Affiliations
- Lodoe Lama
- Laboratory for RNA Molecular Biology, The Rockefeller University
- Carolina Adura
- High-Throughput and Spectroscopy Resource Center, The Rockefeller University
- Wei Xie
- Structural Biology Program, Memorial Sloan-Kettering Cancer Center
- Daisuke Tomita
- Tri-Institutional Therapeutics Discovery Institute
- Taku Kamei
- Tri-Institutional Therapeutics Discovery Institute
- Vitaly Kuryavyi
- Structural Biology Program, Memorial Sloan-Kettering Cancer Center
- Tasos Gogakos
- Laboratory for RNA Molecular Biology, The Rockefeller University
- Joshua I. Steinberg
- Laboratory for RNA Molecular Biology, The Rockefeller University
- Michael Miller
- Tri-Institutional Therapeutics Discovery Institute
- Lavoisier Ramos-Espiritu
- High-Throughput and Spectroscopy Resource Center, The Rockefeller University
- Yasutomi Asano
- Tri-Institutional Therapeutics Discovery Institute
- Shogo Hashizume
- Tri-Institutional Therapeutics Discovery Institute
- Jumpei Aida
- Tri-Institutional Therapeutics Discovery Institute
- Toshihiro Imaeda
- Tri-Institutional Therapeutics Discovery Institute
- Rei Okamoto
- Tri-Institutional Therapeutics Discovery Institute
- Andy J. Jennings
- Tri-Institutional Therapeutics Discovery Institute
- Mayako Michino
- Tri-Institutional Therapeutics Discovery Institute
- Takanobu Kuroita
- Tri-Institutional Therapeutics Discovery Institute
- Andrew Stamford
- Tri-Institutional Therapeutics Discovery Institute
- Pu Gao
- Structural Biology Program, Memorial Sloan-Kettering Cancer Center
- Peter Meinke
- Tri-Institutional Therapeutics Discovery Institute
- J. Fraser Glickman
- High-Throughput and Spectroscopy Resource Center, The Rockefeller University
- Dinshaw J. Patel
- Structural Biology Program, Memorial Sloan-Kettering Cancer Center
- Thomas Tuschl
- Laboratory for RNA Molecular Biology, The Rockefeller University
- DOI
- https://doi.org/10.1038/s41467-019-08620-4
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 14
Abstract
Cyclic GMP-AMP synthase (cGAS) is involved in the modulation of inflammatory responses. Here, the authors present small-molecule inhibitors of human cGAS, characterize their interaction with the protein, and show that the compounds are active in interferon-producing cells including primary human macrophages.
