MFI8 is a small molecule inhibitor of mitochondrial fusion[1].
MFI8 (20 μM; 6 h) reduces significantly mitochondrial aspect ratio with an EC50 of 4.8 μM, and inhibits mitochondrial fusion via mitofusins and subsequently promoting mitochondrial fission[1].
MFI8 possesses functional groups that meet the criteria of the pharmacophore model to interact with mitofusins and promotes mitochondrial fission[1].
MFI8 binds to the HR2 domain of MFN2, modulates MFN conformation and complexes, and alters mitochondrial functionality[1].
MFI8 (0-20 μM; 6 h) concentration-responsively increases caspase-3/7 activity, induces cytochrome c release and decreases membrane potential in a mitofusin-dependent manner. MFI8 also induces DNA damage and induces cell death in combination with BV6 SMAC (second mitochondria-derived activator of caspases) mimetic[1].