1243361-81-0Relevant articles and documents
NAPHTHYRIDINONE COMPOUNDS AS JAK2 V617F INHIBITORS
-
Page/Page column 107-108, (2022/01/04)
The present application provides naphthyridinone compounds that modulate the activity of the V617F variant of JAK2, which are useful in the treatment of various diseases, including cancer.
Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
Chen, Tao,Reich, Nicholas William,Bell, Noah,Finn, Patricia D.,Rodriguez, David,Kohler, Jill,Kozuka, Kenji,He, Limin,Spencer, Andrew G.,Charmot, Dominique,Navre, Marc,Carreras, Christopher W.,Koo-Mccoy, Samantha,Tabora, Jocelyn,Caldwell, Jeremy S.,Jacobs, Jeffrey W.,Lewis, Jason Gustaf
supporting information, p. 7589 - 7613 (2018/09/12)
Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
