] recently defined the inhibitory drug-target interactions of metformin with mammalian respiratory complex I by combining cryo-electron microscopy and enzyme kinetics. The identification of the direct target of metformin’s anticancer effects may help to further investigation for drug development. Second, in in vitro research, the direct effects are emphasized and well-studied, while the indirect effects cannot be mimicked.
]. We expect more in vivo models with more complex designs that are currently used in most in vitro research.There is a discrepancy in the antitumor effect of metformin between clinical research and preclinical studies, although metformin has shown notable benefits for cancer prevention and treatment in preclinical research, and the related molecular mechanisms have been extensively studied.