Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB): A Translational Pharmacodynamic Biomarker for PIKfyve Inhibition With VRG50635.

ABSTRACT: Glycoprotein non-metastatic melanoma protein B (GPNMB) was investigated as a pharmacodynamic (PD) biomarker for PIKfyve inhibition across translational studies ex vivo, in vitro, in animals, and in the clinic, demonstrating significant response to VRG50468 in cells, in vivo in the central nervous system (CNS) and in peripheral fluids and tissues. VRG50468 is the active metabolite of VRG50635, a small molecule PIKfyve inhibitor pro-drug in development for treating amyotrophic lateral sclerosis (ALS). Peripheral pharmacology was evaluated in peripheral blood mononuclear cells (PBMCs) from healthy volunteers ex vivo and in vitro and in PBMCs from mice given oral VRG50635. Central pharmacology was evaluated in vitro using C9orf72 ALS patient-derived induced pluripotent stem cell motor neurons

SUBMITTER: Gontier G 

PROVIDER: S-EPMC12916242 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature