MRK003 / Merck (MSD), Mayo Clinic - LARVOL DELTA

Post-translational modification gene signatures implicate FBXW7 in immune and vascular dysregulation of Moyamoya disease. (PubMed, Front Genet) - "Furthermore, molecular docking and dynamic simulations jointly confirmed the stability of the FBXW7-MRK-003 complex...Especially, we found that FBXW7 and HLA-A bridging immune dysregulation and vascular dysfunction. Our work provide innovative insights into mechanisms of MMD pathogenesis and candidate therapeutic targets for precision therapy of MMD."

Gene Signature • Journal • CNS Disorders • Giant Cell Arteritis • Targeted Protein Degradation • Vascular Neurology • FBXW7

A computational guided, functional validation of a novel therapeutic antibody proposes Notch signaling as a clinical relevant and druggable target in glioma. (PubMed, Sci Rep) - "We functionally assessed the biological effects of the first-in-human tested blocking antibody against Notch1 receptor (brontictuzumab, BRON) in a collection of glioma stem-like cell (GSC) models and compared its effects to genetic Notch1 inhibition as well as classical pharmacological Notch inhibitor treatment using gamma-secretase inhibitor MRK003. We note that the observed phenotype seems only in part due to Notch1 blockage and the drug candidate leads to activation of off target signals. Further studies addressing a possible emergence of therapy resistance due to WNT activation need to be conducted. We further validated our 3D disease modeling technology to be of benefit for drug development projects."

Clinical • Journal • Glioblastoma • Glioma • Oncology • Solid Tumor • HES1 • IDH1 • NOTCH1