A Chemical Probe for the ATAD2 Bromodomain

详细信息    查看全文

• 作者：Dr. Paul Bamborough ; Dr. Chun-wa Chung ; Dr. Emmanuel H. Demont ; Dr. Rebecca C. Furze ; Dr. Andrew J. Bannister ; Dr. Ka Hing Che ; Dr. Hawa Diallo ; Clement Douault ; Dr. Paola Grandi ; Prof. Tony Kouzarides ; Dr. Anne-Marie Michon ; Darren J. Mitchell ; Dr. Rab K. Prinjha ; Dr. Christina Rau ; Dr. Samuel Robson ; Robert J. Sheppard ; Dr. Richard Upton and Dr. Robert J. Watson
• 刊名：Angewandte Chemie
• 出版年：2016
• 出版时间：September 12, 2016
• 年：2016
• 卷：128
• 期：38
• 页码：11554-11558
• 全文大小：2549K
• ISSN：1521-3757

文摘

ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF₂ as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.