Ontology highlight
ABSTRACT:
SUBMITTER: Colombano G
PROVIDER: S-EPMC6437697 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
Colombano Giampiero G Caldwell John J JJ Matthews Thomas P TP Bhatia Chitra C Joshi Amar A McHardy Tatiana T Mok Ngai Yi NY Newbatt Yvette Y Pickard Lisa L Strover Jade J Hedayat Somaieh S Walton Michael I MI Myers Stephanie M SM Jones Alan M AM Saville Harry H McAndrew Craig C Burke Rosemary R Eccles Suzanne A SA Davies Faith E FE Bayliss Richard R Collins Ian I
Journal of medicinal chemistry 20190305 5
A series of imidazo[1,2- b]pyridazin-8-amine kinase inhibitors were discovered to allosterically inhibit the endoribonuclease function of the dual kinase-endoribonuclease inositol-requiring enzyme 1α (IRE1α), a key component of the unfolded protein response in mammalian cells and a potential drug target in multiple human diseases. Inhibitor optimization gave compounds with high kinome selectivity that prevented endoplasmic reticulum stress-induced IRE1α oligomerization and phosphorylation, and i ...[more]