A first-in-class natural compound that induces mitophagy both in vitro and in vivo following oral consumption; prevents the accumulation of dysfunctional mitochondria with age and extends lifespan in C. elegans, improves exercise capacity in mouse models of age-related decline of muscle function.

U0126, an effective and selective non-competitive inhibitor of MAP kinase, inhibits MEK-1 and MEK-2 with IC50 values of 0.07 and 0.06 μM respectively. U0126 inhibits autophagy and mitophagy.

P62-mediated mitophagy inducer (PMI) is a small molecule p62-mediated mitophagy inducer that activates mitophagy without recruiting Parkin or collapsing membrane potential and retains activity in cells devoid of a fully functional PINK1/Parkin pathway; induces doubling NQO1 activity at 1 uM, and upregulates Nrf2 and ARE-dependent antioxidant genes; increases the expression and signaling of the autophagic adaptor molecule P62/SQSTM1 and forces mitochondria into autophagy; disrupts the Nrf2-Keap1 interaction.