Ontology highlight
ABSTRACT:
SUBMITTER: Tan L
PROVIDER: S-EPMC5484537 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Tan Li L Gurbani Deepak D Weisberg Ellen L EL Hunter John C JC Li Lianbo L Jones Douglas S DS Ficarro Scott B SB Mowafy Samar S Tam Chun-Pong CP Rao Suman S Du Guangyan G Griffin James D JD Sorger Peter K PK Marto Jarrod A JA Westover Kenneth D KD Gray Nathanael S NS
Bioorganic & medicinal chemistry 20161209 3
TAK1 (transforming growth factor-β-activated kinase 1) is an essential intracellular mediator of cytokine and growth factor signaling and a potential therapeutic target for the treatment of immune diseases and cancer. Herein we report development of a series of 2,4-disubstituted pyrimidine covalent TAK1 inhibitors that target Cys174, a residue immediately adjacent to the 'DFG-motif' of the kinase activation loop. Co-crystal structures of TAK1 with candidate compounds enabled iterative rounds of ...[more]