Phenformin (hydrochloride)

834-28-6

241.72

DMSO : 1 mg/mL (4.14 mM; ultrasonic and adjust pH to 2 with 1M HCl); DMF : < 1 mg/mL (insoluble); H2O : 12.5 mg/mL (51.71 mM; Need ultrasonic); Ethanol : < 1 mg/mL (insoluble)

Autophagy; Epigenetics; PI3K/Akt/mTOR

Phenformin hydrochloride is an anti-diabetic drug from the biguanide class, can activate AMPK activity. IC50 & Target: AMPK^[2] In Vitro: Phenformin stimulates the phosphorylation and activation of AMPKalpha1 and AMPKalpha2 without altering LKB1 activity^[1]. 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]^[2]. 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^[3]. 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^[4]. Phenformin-treated rats reveals a tendency towards a decrease in blood insulin level (radioimmunoassay)^[5]. In Vivo: Phenformin increases levels of P-eIF2alpha and its target BiP/Grp78 in normal lung as well as in lung tumors of mice^[3].