Phenformin HCl

In vitro: Phenformin stimulates the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity. Phenformin increases AMPK activity and phosphorylation in the isolated heart, the increase in AMPK activity is always preceded by and correlated with increased cytosolic [AMP]. Phenformin is a 50-fold more potent inhibitor of mitochondrial complex I than metformin. Phenformin robustly induces apoptosis in LKB1 deficient NSCLC cell lines. Phenformin at 2 mM similarly induces AMPK signaling as shown by increased P-AMPK and P-Raptor levels. Phenformin induces higher levels of cellular stress, triggering induction of P-Ser51 eIF2alpha and its downstream target CHOP, and markers of apoptosis at later times. Phenformin induces a significant increase in survival and therapeutic response in KLluc mice following long-term treatment. Phenformin and AICAR increases AMPK activity in H441 cells in a dose-dependent fashion, stimulating the kinase maximally at 5-10 mm and 2 mm, respectively. Phenformin significantly decreases basal ion transport (measured as short circuit current) across H441 monolayers by approximately 50% compared with that of controls. Phenformin and AICAR significantly reduce amiloride-sensitive transepithelial Na+ transport compared with controls. Phenformin and AICAR suppress amiloride-sensitive Na+ transport across H441 cells via a pathway that includes activation of AMPK and inhibition of both apical Na+ entry through ENaC and basolateral Na+ extrusion via the Na+, K+-ATPase. Phenformin-treated rats reveals a tendency towards a decrease in blood insulin level (radioimmunoassay). In vivo: Phenformin also increases levels of P-eIF2alpha and its target BiP/Grp78 in normal lung as well as in lung tumors of mice.

Phenethylbiguanide hydrochloride

C10H15N5.HCl

0, 9965