5-methoxyflavone

5-methoxyflavone (5-MF) is a naturally occurring O-methylated flavonoid compound being investigated for its potential therapeutic benefits in metabolic, neurodegenerative, and oncological disorders. In metabolic health, 5-methoxyflavone acts as a dual agonist of the estrogen-related receptors alpha (ERRα) and gamma (ERRγ), which upregulates peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression via cAMP-dependent signaling. This dual activation enhances mitochondrial function, promotes the browning of white adipose tissue, and improves glucose tolerance and metabolic resilience in preclinical models of obesity and type 2 diabetes. Additionally, 5-methoxyflavone has been identified as a selective inhibitor of DNA polymerase beta (DNA pol-β), demonstrating neuroprotective effects against beta-amyloid toxicity by preventing ectopic cell-cycle reactivation and subsequent apoptosis in primary neurons. In oncology, it has shown anti-proliferative and pro-apoptotic activity in lung adenocarcinoma models by inhibiting the PI3K/AKT/GSK3β signaling pathway and downregulating PD-L1 expression. It also targets cytochrome P450 1A1 (CYP1A1) to alleviate hepatic steatosis in models of non-alcoholic fatty liver disease (NAFLD).

Other names

5-MF5-methoxy-2-phenyl-4H-chromen-4-one5-methoxy-2-phenylchromen-4-one5MF