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.
Adipose triglyceride lipase (ATGL), a central mediator of triglyceride hydrolysis and fatty acid mobilization, modulates hepatic lipid homeostasis and metabolic signaling pathways that contribute to the activation of fibrogenic responses.
Researchers from Ospedale San Raffaele presented the preclinical characterization of SR-1891, a long-acting capsid assembly modulator (CAM) in models of chronic hepatitis B. In Hepa D38 cells, the compound exhibited EC50 and EC90 values of 0.2 and 0.8 nM, respectively, without any detectable cytotoxicity.
Minneapolis-based Celcuity Inc. was like the Rolling Stones at the 2026 American Society of Clinical Oncology annual meeting. The company reported positive phase III data for its pan-PI3K/mTORC1/2 inhibitor gedatolisib, but Celcuity (NASDAQ:CELC) couldn’t get any satisfaction from investors who sent shares down 25.7%, or $31.54, to $91.42 on June 2, 2026.
At the 2026 American Society of Clinical Oncology annual meeting, multiple companies presented data for their drugs targeting WEE1, a checkpoint for the transition from G2 into mitosis. Aprea Therapeutics Inc. presented phase 1 data for its WEE1 inhibitor APR-1051 in patients with advanced solid tumors showing two patients with endometrial cancers achieved partial responses in the dose-escalation study. Likewise, Zentalis Pharmaceuticals Inc. had tantalizing early results from a phase Ib study showing azenosertib plus paclitaxel in patients with platinum-resistant ovarian cancer produced an overall response rate of 39% with a median progression-free survival of 7.3 months.
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.
Several presentations at EASL highlight a new generation of therapies coming into view, with the work from Tune Therapeutics Inc. standing out as one of the most relevant for the novelty it represents and the step forward it signals. The company is investigating the use of TUNE-401 as a potential treatment for hepatitis B.
At the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Revolution Medicines Inc. followed up its stellar top-line data with the details from the phase III RASolute 302 study of its pan-RAS inhibitor daraxonrasib in patients with previously treated, metastatic pancreatic ductal adenocarcinoma. The results were simultaneously published in The New England Journal of Medicine.