Article
Discovery of DNL343: A Potent, Selective, and Brain-Penetrant eIF2B Activator Designed for the Treatment of Neurodegenerative Diseases.
Journal of medicinal chemistry - 11 Apr 2024
Craig Robert A, De Vicente Javier, Estrada Anthony A, Feng Jianwen A, Lexa Katrina W, Canet Mark J, Dowdle William E, Erickson Rebecca I, Flores Brittany N, Haddick Patrick C G, Kane Lesley A, Lewcock Joseph W, Moerke Nathan J, Poda Suresh B, Sweeney Zachary, Takahashi Ryan H, Tong Vincent, Wang Jing, Yulyaningsih Ernie, Solanoy Hilda, Scearce-Levie Kimberly, Sanchez Pascal E, Tang Liwei, Xu Musheng, Zhang Rui, Osipov Maksim
Abstract excerpt
Eukaryotic translation initiation factor 2B (eIF2B) is a key component of the integrated stress response (ISR), which regulates protein synthesis and stress granule formation in response to cellular insult. Modulation of the ISR has been proposed as a therapeutic strategy for treatment of neurodegenerative diseases such as vanishing white matter (VWM) disease and amyotrophic lateral sclerosis (ALS) based on its...
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