IDO1 Inhibitor / Merck (MSD) - LARVOL DELTA

TRYPTOPHAN DEPRIVATION DUE TO INCREASED IDO-1 TRIGGERS A METABOLIC ADAPTIVE RESPONSE AND DOWN-REGULATES CD38 IN MULTIPLE MYELOMA (EHA 2019) - "In zebrafishes IDO inhibitor epacadostat could not delay MM engraftment. Increased doses of epacadostat (range 500-1000 nM) were cytotoxic against both human T-CD4+cells and T-CD8+ cells and for this reason could not be further tested in pre-clinical in-vivo models.Conclusion Trp shortage is associated to progression from MGUS through MM due to increased IDO, contributing to metabolic adaptation. However, other soluble factors are involved in co-opting adaptive metabolic phenotype, since IDO inhibition is not sufficient to delay MM engraftment in vivo."

IO Biomarker