DNL747

DNL747 is an orally available, brain-penetrant small molecule inhibitor of receptor-interacting serine/threonine-protein kinase 1 (RIPK1). RIPK1 is a key signaling protein in the tumor necrosis factor (TNF) receptor pathway and regulates inflammation and cell death, particularly necroptosis, which is implicated in neurodegenerative diseases. By inhibiting RIPK1, DNL747 was developed to reduce neuroinflammation and neuronal cell death associated with conditions such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis. The drug was co-developed by Denali Therapeutics and Sanofi based on foundational research from Harvard University. Clinical trials demonstrated that DNL747 was generally safe and well tolerated at tested doses but did not achieve sufficient target inhibition at tolerable doses; higher exposures were limited by toxicity concerns. As a result, development for all indications has been discontinued[2][4][5][6].

Other names

SAR443060SAR-443060SAR 443060