Transforming growth factor-β-activated kinase 1 (TAK1) is a crucial central signaling molecule of hepatic cell death, inflammation and fibrogenesis through NF-κB and MAPK in metabolic dysfunction-associated steatotic liver disease (MASLD). Its pharmacological inhibition using the TAK1 inhibitor HS-276 was tested in vivo in a murine model of diet-induced MASLD.
There is a growing consensus that alcohol-related liver disease (ALD) should be considered a metabolic disorder under the influence of the gut-liver axis. Metabolome data have highlighted fatty acid-activated G protein-coupled receptors (GPCRs) as the main affected pathways, where the relationship of G-protein-coupled receptor 119 (GPR119) with ALD remains unexplored.
Alterations in PNPLA3, particularly the I148M variant, impair lipid metabolism in hepatocytes, leading to lipid accumulation and driving progression from steatosis to fibrosis and cirrhosis. Targeting this genetic driver may offer a strategy to reduce steatosis and limit disease progression.
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipid accumulation in the liver and inflammation. Sterol O-acyltransferase 2 (SOAT2) is a key enzyme in intestinal absorption and hepatic secretion of cholesterol. PRD Therapeutics Inc. has developed PRD-001, a selective SOAT2 inhibitor currently in phase I trials for MASH.
Muna Therapeutics Aps has patented new dihydropyrrolopyrimidinone compounds acting as triggering receptor expressed on myeloid cells 2 (TREM2) agonists potentially useful for the treatment of osteoporosis, rheumatoid arthritis, systemic lupus erythematosus, type 2 diabetes, obesity, metabolic dysfunction-associated steatotic liver disease (MASLD; NAFLD), neurodegeneration and inflammatory bowel disease, among others.
Deep Apple Therapeutics Inc. has divulged new alkylphenyl substituted compounds acting as gastric inhibitory polypeptide receptor (GIPR) antagonists potentially useful for the treatment of obesity and type 2 diabetes.
Zhongshan Laibo Ruichen Biomedicine Co. Ltd. has patented new polypeptides and their drug conjugates potentially useful for the treatment of osteoporosis.
Protuoso Biosciences has announced the close of an oversubscribed $9.5 million seed financing round, the proceeds of which will be used to advance its multifunctional protein engineering platform and broad pipeline across cardiometabolic, oncology and autoimmune diseases.
Merck Sharp & Dohme LLC (MSD) has disclosed new glucagon-like peptide 1 receptor (GLP-1R) agonists potentially useful for the treatment of obesity and type 2 diabetes.
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