Compound 147 is a preferential activator of the ER stress sensing protein ATF6. It was able to selectively reduce secretion and extracellular aggregation of destabilized amyloidogenic variants of TTR and LC proteins. Compound 147-dependent ATF6 activation proceeds via metabolic activation to a...
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Compound 147 is a preferential activator of the ER stress sensing protein ATF6. It was able to selectively reduce secretion and extracellular aggregation of destabilized amyloidogenic variants of TTR and LC proteins. Compound 147-dependent ATF6 activation proceeds via metabolic activation to a reactive electrophile that selectively modifies ER proteins including multiple protein disulfide isomerases. Compound 147 suppressed pluripotency and promoted human stem cell differentiation toward a mesodermal lineage via ER expansion. It protected the heart against ischemia/reperfusion (I/R) injury in a mouse model of acute myocardial infarction in an ATF6-dependent manner. Brain, kidney, and liver tissue was also protected from I/R damage and impaired proteostasis. Compound 147 reduced infection of multiple strains of dengue and Zika viruses in an ATF6-independent manner
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