Buformin hydrochloride (NSC-528218; NSC528218; 1-butylbiguanide) is an orally available AMPK activator used as an antidiabetic drug belonging to the biguanide class. It is chemically/structurally related to metformin and phenformin. Buformin acts by decreasing hepatic gluconeogenesis and lowering blood glucose production in vivo. Buformin was marketed by Grünenthal (a German pharmaceutical company) as Silubin. Buformin delays absorption of glucose from the gastrointestinal tract, increases insulin sensitivity and glucose uptake into cells, and inhibits synthesis of glucose by the liver. Buformin and the other biguanides are not hypoglycemic, but rather antihyperglycemic agents. They do not produce hypoglycemia; instead, they reduce basal and postprandial hyperglycemia in diabetics.[5] Biguanides may antagonize the action of glucagon, thus reducing fasting glucose levels.
Physicochemical Properties
| Molecular Formula | C6H16CLN5 |
| Molecular Weight | 193.68 |
| Exact Mass | 193.109 |
| CAS # | 1190-53-0 |
| Related CAS # | Buformin;692-13-7 |
| PubChem CID | 84976 |
| Appearance | Light yellow to green yellow solid powder |
| Boiling Point | 322.7ºC at 760 mmHg |
| Melting Point | 174-177ºC |
| Flash Point | 148.9ºC |
| Vapour Pressure | 0.000275mmHg at 25°C |
| LogP | 2.277 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 1 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 12 |
| Complexity | 156 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | KKLWSPPIRBIEOV-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C6H15N5.ClH/c1-2-3-4-10-6(9)11-5(7)8/h2-4H2,1H3,(H6,7,8,9,10,11)1H |
| Chemical Name | 1-Butylbiguanide monohydrochloride |
| Synonyms | NSC 528218 Silubin NSC-528218Buformin hydrochloride NSC528218 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | The concentration-dependent inhibition of SKBR3 and BT474 cell growth is observed with buformin hydrochloride (0-10 mM; 5 days); IC50s for erbB-2-overexpressing SKBR3 and BT474 cells are 246.7 μM and 98.6 μM, respectively [1]. Buformin hydrochloride (0–3 mM; 48 hours) reduces the percentage of cells in the S phase and raises the proportion of cells in the G0/G1 phase, particularly in SKBR3 cells [1]. As well as inhibiting Akt activation/phosphorylation in SKBR3 and BT474 cells, buformin hydrochloride (0-3 mM; 24 hours) inhibits RTK activation, including downstream erbB-2 and IGF1R signaling [1]. |
| ln Vivo | In MMTV-erbB-2 transgenic mice, buformin hydrochloride (oral; 7.6 mmol/kg, mixed in diet; 7 days) dramatically lowers tumor volume and weight and inhibits the growth and morphogenesis of the mammary glands [1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: ErbB-2-overexpressing SKBR3 and BT474 cells Tested Concentrations: 0 μM, 1 μM, 3 μM, 10 μM, 30 μM, 100 μM, 300 μM, 1, 3, or 10 mM Incubation Duration: 5 days Experimental Results: decreased cell viability in erbB-2-overexpressing breast cells. Cell Cycle Analysis[1] Cell Types: ErbB-2-overexpressing SKBR3 and BT474 cells Tested Concentrations: 0.5 mM; 1 mM; 3 mM Incubation Duration: 48 hrs (hours) Experimental Results: Increased cells arresting in G0/G1 phase. Western Blot Analysis[1] Cell Types: ErbB-2-overexpressing SKBR3 and BT474 cells Tested Concentrations: 0mM, 0.1mM, 0.3mM, 1mM, or 3mM Incubation Duration: 24 hrs (hours) Experimental Results: diminished p-AMPK, p-p706S, p-ERK1/2 expression in a concentration-dependent manner. |
| Animal Protocol |
Animal/Disease Models: Female MMTV-erbB-2 transgenic mice[1] Doses: 7.6 mmol/kg Route of Administration: Oral administration; 7 days Experimental Results: Inhibited mammary syngeneic tumor growth in MMTV-erbB-2 transgenic mice. |
| References |
[1]. Buformin hydrochloride 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]. Buformin hydrochloride 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. |
| Additional Infomation |
Buformin Hydrochloride is the hydrochloride salt form of buformin, an agent belonging to the biguanide class of antidiabetics with antihyperglycemic activity. Buformin is not metabolized and is excreted in the urine. This agent has an elevated risk of causing lactic acidosis, and has been withdrawn from the market. An oral hypoglycemic agent that inhibits gluconeogenesis, increases glycolysis, and decreases glucose oxidation. |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~125 mg/mL (~645.39 mM) H2O : ~100 mg/mL (~516.32 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (10.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (516.32 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.1632 mL | 25.8158 mL | 51.6316 mL | |
| 5 mM | 1.0326 mL | 5.1632 mL | 10.3263 mL | |
| 10 mM | 0.5163 mL | 2.5816 mL | 5.1632 mL |