(original) (raw)

TY - JOUR AU - Nicodeme, Edwige AU - Jeffrey, Kate L. AU - Schaefer, Uwe AU - Beinke, Soren AU - Dewell, Scott AU - Chung, Chun-wa AU - Chandwani, Rohit AU - Marazzi, Ivan AU - Wilson, Paul AU - Coste, Hervé AU - White, Julia AU - Kirilovsky, Jorge AU - Rice, Charles M. AU - Lora, Jose M. AU - Prinjha, Rab K. AU - Lee, Kevin AU - Tarakhovsky, Alexander PY - 2010 DA - 2010/12/01 TI - Suppression of inflammation by a synthetic histone mimic JO - Nature SP - 1119 EP - 1123 VL - 468 IS - 7327 AB - Small molecules that perturb chromatin proteins are an emerging focus of current biomedical research. Two groups reporting in this issue have targeted bromodomain-containing BET proteins that bind acetylated lysine residues during gene activation, arriving at cell-permeable small molecule compounds with similar structures based on fused triazole-diazepine rings. James Bradner and colleagues report the development of a compound named JQ1. The BET protein BRD4, with two bromodomains, is implicated in human squamous cell carcinoma. JQ1 inhibits the growth of BRD4-dependent tumours in mouse models. Alexander Tarakhovsky and colleagues' inhibitor, I-BET, is shown to interfere with the binding of certain BET family members to acetylated histones. It inhibits activation of pro-inflammatory genes in macrophages and has immunomodulatory activity in a mouse model of inflammatory disease. SN - 1476-4687 UR - https://doi.org/10.1038/nature09589 DO - 10.1038/nature09589 ID - Nicodeme2010 ER -