SMIP004-7

SMIP004-7 is a small molecule inhibitor of mitochondrial respiration with selective in vivo anti-cancer activity. It is an active analog of SMIP004, originally identified as an inducer of cancer-cell selective apoptosis. SMIP004-7 targets drug-resistant cancer cells with stem-like features, such as breast cancer stem-like cells (BCSCs), by inhibiting mitochondrial respiration complex I (NADH:ubiquinone oxidoreductase). Unlike most complex I inhibitors that target the quinone-binding site, SMIP004-7 and its cytochrome P450-dependent activated metabolites act via an uncompetitive mechanism of inhibition involving a distinct N-terminal region of the catalytic subunit NDUFS2, leading to rapid disassembly of complex I. This inhibition of oxidative phosphorylation (OXPHOS) suppresses oxygen consumption, induces aerobic glycolysis, and triggers oxidative stress, selectively killing cancer stem cells and inhibiting the growth of triple-negative breast cancer (TNBC) and prostate cancer transplants in vivo.

Other names

2-Methyl-4-butylaniline4-Butyl-2-methylaniline4-Butyl-2-methylbenzenamineN-(4-butyl-2-methyl-phenylaniline)N-(4-butyl-2-methylphenyl)aniline