2-(4-chlorophenoxy)-N-(4-(2-(4-chlorophenoxy)acetamido)cyclohexyl)acetamide

BeschreibungISRIB (integrated stress response inhibitor) is an experimental drug that reverses the effects of eIF2α phosphorylation with an IC50 of 5 nM. It was discovered in the laboratory of Peter Walter at University of California, San Francisco (UCSF) through a semi-automated screening of a large library of small molecules by Carmela Sidrauski, who decided to pursue research on it. It has been shown to inhibit eIF2α phosphorylation-induced stress granule (SG) formation. Since eIF2α phosphorylation is known to be involved in memory formation, ISRIB was tested to see whether it would be active in vivo, and was found to readily cross the blood-brain barrier, with a half-life of eight hours.

VerwendenISRIB (mix-Isomer), is a symmetric bis-glycolamide that inhibits integrated stress response (ISR). In wild-type mice studies has shown that it improved memory by efficiently reversing the effects of eIF2α phosphorylation, which has brought expectation that inhibition of PERK signaling may have the potential to ameliorate Alzheimer's disease. In a present study ISRIB demonstrated to attenuate amyloid b-induced neuronal cell death although the pharmacological mechanisms of this action have not yet been elucidated.