Ontology highlight
ABSTRACT:
SUBMITTER: Henise JC
PROVIDER: S-EPMC3663048 | biostudies-literature | 2011 Jun
REPOSITORIES: biostudies-literature
Henise Jeffrey C JC Taunton Jack J
Journal of medicinal chemistry 20110531 12
A structure-based approach was used to design irreversible, cysteine-targeted inhibitors of the human centrosomal kinase, Nek2. Potent inhibition of Nek2 kinase activity in biochemical and cell-based assays required a noncatalytic cysteine residue (Cys22), located near the glycine-rich loop in a subset of human kinases. Elaboration of an oxindole scaffold led to our most selective compound, oxindole propynamide 16 (JH295). Propynamide 16 irreversibly inhibited cellular Nek2 without affecting the ...[more]