Buformin

Buformin (1-Butylbiguanide) is a potent and orally active biguanide antidiabetic agent, an AMPK activator. Buformin decreases hepatic gluconeogenesis and lowers blood glucose production in vivo. Buformin also has anti-cancer activities and is applied in cancer study (such as, cervical cancer and breast cancer, et al)[1].

Signaling Pathways >> Epigenetics >> AMPK

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

Research Areas >> Metabolic Disease

Buformin (0-10 mM; 5 days) inhibits SKBR3 and BT474 cells growth as a concentration-dependent manner, exhibits IC50 values of 246.7 μM and  98.6 μM for erbB-2-overexpressing SKBR3 and BT474 cells, respectively[1]. Buformin (0-3 mM; 48 hours)  increases the percentage of cells in G0/G1 phase and reduced the percentage of cells in S phase, especially in the SKBR3 cells[1]. Buformin (0-3 mM; 24 hours) suppresses RTK activation, including erbB-2 and IGF1R signaling  downstream, and Akt activation/phosphorylation is inhibited in both SKBR3 and BT474 cells[1]. Cell Viability Assay[1] Cell Line: ErbB-2-overexpressing SKBR3 and BT474 cells Concentration: 0 μM, 1 μM, 3 μM, 10 μM, 30 μM, 100 μM, 300 μM, 1, 3, or 10 mM Incubation Time: 5 days Result: Reduced cell viability in erbB-2-overexpressing breast cells. Cell Cycle Analysis[1] Cell Line: ErbB-2-overexpressing SKBR3 and BT474 cells Concentration: 0.5 mM; 1 mM; 3 mM Incubation Time: 48 hours Result: Increased cells arresting in G0/G1 phase. Western Blot Analysis[1] Cell Line: ErbB-2-overexpressing SKBR3 and BT474 cells Concentration: 0 mM, 0.1 mM, 0.3 mM, 1 mM, or 3 mM Incubation Time: 24 hours Result: Decreased p-AMPK, p-p706S, p-ERK1/2 expression in a concentration-dependent manner.

Buformin (oral administation; 7.6 mmol/kg of chow; 7 days) exhibits significantly reduced tumor volumes and weights, and hinders mammary morphogenesis and proliferation in MMTV-erbB-2 transgenic mice[1] Animal Model: Female MMTV-erbB-2 transgenic mice[1] Dosage: 7.6 mmol/kg Administration: Oral administation; 7 days Result: Inhibited mammary syngeneic tumor growth in MMTV-erbB-2 transgenic mice.

[1]. Amanda B Parris, et al. Buformin Inhibits the Stemness of erbB-2-overexpressing Breast Cancer Cells and Premalignant Mammary Tissues of MMTV-erbB-2 Transgenic Mice. J Exp Clin Cancer Res

[2]. Jing Li, et al. Buformin Suppresses Proliferation and Invasion via AMPK/S6 Pathway in Cervical Cancer and Synergizes With Paclitaxel. Cancer Biol Ther. 2018 Jun 3;19(6):507-517.

DATA ITEMS CITED :

3

MOLECULAR FORMULA :

C6-H15-N5

MOLECULAR WEIGHT :

157.26

WISWESSER LINE NOTATION :

MUYZMYUM&M4

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 24,1521,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

140 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 24,1521,1981

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

18 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

MEXPAG Medicina Experimentalis. (Basel, Switzerland) V.1-11, 1959-64; V.18-19, 1968-69. For publisher information, see JNMDBO. Volume(issue)/page/year: 8,237,1963