MP201

MP201 is an orally available small-molecule prodrug of the mitochondrial uncoupler 2,4-dinitrophenol (DNP, also known as MP101), being developed by Mitochon Pharmaceuticals for neurodegenerative and neurotraumatic indications including Parkinson’s disease, traumatic brain injury, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and optic neuritis.[1][5][11][13] Chemically, MP201 carries a carbon-chain linker on the hydroxyl group of DNP that renders it inactive until enzymatic cleavage in the portal circulation releases the active parent, thereby slowing absorption, reducing Cmax, and extending exposure compared with DNP while aiming to improve safety.[1][9][11] By inducing mild mitochondrial uncoupling, MP201 decreases mitochondrial membrane potential and reactive oxygen species production and triggers adaptive bioenergetic stress responses involving CREB, PGC‑1α, NF‑κB, BDNF, SOD2, TFAM, and other stress-resistance and neuroplasticity pathways, leading to neuroprotection in rodent models of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis (including optic neuritis), traumatic brain injury, and blast-induced brain injury.[1][2][11][13] In preclinical studies, once-daily oral MP201 preserves dopaminergic neurons, retinal ganglion cells, myelination, and cognitive function, and improves mitochondrial respiration and oxidative stress markers; human dosing and clinical efficacy have not yet been established.[1][2][5][11][13]

Other names

2,4-dinitrophenol prodrug