Ontology highlight
ABSTRACT:
SUBMITTER: Bamborough P
PROVIDER: S-EPMC7314595 | biostudies-literature | 2016 Sep
REPOSITORIES: biostudies-literature
Bamborough Paul P Chung Chun-Wa CW Demont Emmanuel H EH Furze Rebecca C RC Bannister Andrew J AJ Che Ka Hing KH Diallo Hawa H Douault Clement C Grandi Paola P Kouzarides Tony T Michon Anne-Marie AM Mitchell Darren J DJ Prinjha Rab K RK Rau Christina C Robson Samuel S Sheppard Robert J RJ Upton Richard R Watson Robert J RJ
Angewandte Chemie (International ed. in English) 20160817 38
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. ...[more]