Mito-LND (Mito-lonidamine) is a tumor-selective inhibitor of oxidative phosphorylation with IC50 of 1.2 and 2.4 uM for mitochondrial complexes I and II, respectively, impacts the activity of mitochondrial complexes, ROS generation and peroxiredoxin oxidation.
Mito-LND shows 100-fold more potent than lonidamine (LND).
Mito-LND inhibits mitochondrial bioenergetics in lung cancer cells and mitigates lung cancer cell viability, growth, progression, and metastasis of lung cancer xenografts in mice.
Mito-LND blocks lung tumor development and brain metastasis by inhibiting mitochondrial bioenergetics, stimulating the formation of reactive oxygen species, oxidizing mitochondrial peroxiredoxin, inactivating AKT/mTOR/p70S6K signaling, and inducing autophagic cell death in lung cancer cells.
Mito-LND is selective for cancer cells and tumor tissue, does not induce autophagy in normal lung and brain tissue or normal lung cell lines.