M30-E05 is a small molecule inhibitor of apoptosis-inducing factor/coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (AIP/CHCHD4) interaction, binds to NADH pocket of AIF (−8.5 ± 0.7 kcal/mol, human AIF), preventing AIF dimerization and disrupting the AIF/CHCHD4 complex.
M30-E05 also shows preferential binding on murine AIF on NAD binding pocket (−9.0 ± 0.7 kcal/mol).
M30-E05 exhibits cytotoxicity on different osteosarcoma cell lines, including both parental and drug-resistant cell lines (HOS, HOS-R/DOXO, HOS-R/MTX, MG63, U2OS, 143B, SAOS2, and SAOS-R/MTX), with IC50 of about 10 uM.
M30-E05 reduces viability of several tumor cell lines derived from ovarian cancer (both parental and drug-resistant cell lines), lung cancer, pancreatic cancer, as well as leukemia with IC50 of 2-3 uM.
M30-E05 could overcome doxorubicin and methotrexate resistance.
M30-E05 induces AIF-independent apoptosis and caspase activations in HOS cell line, perturbs mitochondrial respiratory chain biogenesis and mitochondrial calcium homeostasis.
M30-E05 shows reduced viability in secondary cultured in vitro patient-derived xenografts (PDX) with IC50 of 17-40 uM.
M30-E05 (10-100 mg/kg, oral, vehicle: 0.5% methylcellulose) inhibits tumor growth in GR-OS-18 engrafted NSG mice.