Ontology highlight
ABSTRACT:
SUBMITTER: Okoye-Okafor UC
PROVIDER: S-EPMC5155016 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
Okoye-Okafor Ujunwa C UC Bartholdy Boris B Cartier Jessy J Gao Enoch N EN Pietrak Beth B Rendina Alan R AR Rominger Cynthia C Quinn Chad C Smallwood Angela A Wiggall Kenneth J KJ Reif Alexander J AJ Schmidt Stanley J SJ Qi Hongwei H Zhao Huizhen H Joberty Gerard G Faelth-Savitski Maria M Bantscheff Marcus M Drewes Gerard G Duraiswami Chaya C Brady Pat P Groy Arthur A Narayanagari Swathi-Rao SR Antony-Debre Iléana I Mitchell Kelly K Wang Heng Rui HR Kao Yun-Ruei YR Christopeit Maximilian M Carvajal Luis L Barreyro Laura L Paietta Elisabeth E Makishima Hideki H Will Britta B Concha Nestor N Adams Nicholas D ND Schwartz Benjamin B McCabe Michael T MT Maciejewski Jaroslav J Verma Amit A Steidl Ulrich U
Nature chemical biology 20151005 11
Neomorphic mutations in isocitrate dehydrogenase 1 (IDH1) are driver mutations in acute myeloid leukemia (AML) and other cancers. We report the development of new allosteric inhibitors of mutant IDH1. Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants. Treatment of IDH1 mutant primary AML cells ...[more]