GW493838 / GSK - LARVOL DELTA

Identification of molecular targets from the interactome of primary sclerosing cholangitis and their therapeutic modulation (EASL 2026) - "GW-493838 combined with BMS270394 notably downregulated both TGF-beta and Notch signatures... In advanced human PSC we discovered a range of molecular targets - by multi-molecular approaches, a reduced number of potential targets – selected by Mdr2-/- animal model validation and in silico drug screening. Finally, disease-modulating effects of of these predicted small molecules were investigated using PSC patient-derived cholangiocyte organoids suggesting NRP1 and THBS1 as relevant therapeutic targets. OP and CF share first authorship; MT and TR share senior authorship"

Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • ABCB4 • CD1C • CD36 • ITGAX • KRT19 • NFKB1 • NRP1 • SCARB1 • SLIT2 • TGFB1

Identification of molecular targets from the interactome of primary sclerosing cholangitis and their therapeutic modulation (FFS-AIH 2025) - "In silico screening identified their ligands BGB-283 and RAF-265, which downregulated NF-kB signature expression in PSC organoids. GW-493838 combined with BMS270394 notably downregulated both TGF-beta and Notch signatures. We discovered perspective molecular targets in PSC and showed the impact of their predicted small molecule ligands on transcriptomes of primary PSC cholangiocyte organoids. OP and CF share first authorship MT and TR share senior authorship"

Cholestasis • Fibrosis • Gastroenterology • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Primary Biliary Cholangitis • ABCB4 • CD1C • CD36 • ITGAX • KRT19 • NFKB1 • NRP1 • SCARB1 • SLIT2 • TGFB1 • VEGFA