Blocking the DRP1-FIS1 interaction for diseases with mitochondrial dysfunction

A small molecule inhibitor disrupting the interaction between DRP1 and FIS1, mitochondrial proteins that promote mitochondrial fission and subsequent metabolic dysfunction and cell death during inflammatory cellular stress, could help treat diseases such as sepsis, neurodegeneration, and ischemia, without interfering with normal mitochondrial function. 

In silico screening for small molecules with drug-like properties that bind to the same switch I-adjacent grove (SWAG) allosteric site on DRP1 as a previously identified peptide inhibitor of the DRP1-FIS1 interaction, with greater stability and oral bioavailability than the peptide, identified a compound that inhibited in vitro DRP1 GTPase activity with an IC50 of 270 nM. ...