IVO-21

IVO-21 is an oral small-molecule mitochondrial stabilizer being developed by the National Institutes of Health (NIH) in collaboration with the Solve ME/CFS Initiative. It acts as an inhibitor of voltage-dependent anion-selective channel protein 1 (VDAC1) oligomerization by selectively binding to over-oxidized cysteine 127 (C127) of VDAC1. This action prevents VDAC1 oligomerization and disrupts the VDAC1-HK2 (hexokinase-2) interaction, thereby restoring mitochondrial energy production, reducing glycolysis, and mitigating the release of mitochondrial DNA (mtDNA) and pro-inflammatory cytokines. IVO-21 is being investigated as a potential therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), Long COVID, and other conditions associated with mitochondrial dysfunction and chronic inflammation.