Size | Price | Stock | Qty |
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1g |
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5g |
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10g |
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25g |
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50g |
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Other Sizes |
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Purity: ≥98%
Phenformin HCl (ST-50409947; D-08352; W-104144), the hydrochloride salt of phenformin, was a marketed anti-diabetic drug of the biguanide class, but was withdrawn from most markets in the late 1970s due to a high risk of lactic acidosis. It works as an AMP-activated protein kinase (AMPK) activator to reduce blood glucose levels in people with non-insulin-dependent diabetes mellitus. Inhibiting complex 1 of the mitochondrial respiratory chain and activating AMP-activated protein kinase (AMPK)-dependent signaling are the mechanisms by which phenformin increases insulin sensitivity and reduces insulin resistance.
Targets |
AMPK
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ln Vitro |
Without affecting LKB1 activity, phenformin increases the phosphorylation and activation of AMPKalpha1 and AMPKalpha2. [1] In the isolated heart, phenformin increases AMPK activity and phosphorylation; the increase in AMPK activity is always preceded by and correlated with increased cytosolic [AMP]. [2] In comparison to metformin, phenformin has a 50-fold higher inhibitory potency of mitochondrial complex I. In LKB1 deficient NSCLC cell lines, phenformin strongly induces apoptosis. Increased P-AMPK and P-Raptor levels demonstrate that phenformin at 2 mM similarly induces AMPK signaling. Higher levels of cellular stress brought on by phenformin result in the later induction of P-Ser51 eIF2, its downstream target CHOP, and markers of apoptosis. Following prolonged treatment with phenformin, KLluc mice exhibit a significantly higher rate of survival and therapeutic response.[3] AICAR and phenformin both increase AMPK activity in H441 cells in a dose-dependent manner, with maximal stimulation occurring at 2 mm and 5-10 mm, respectively. Phenformin significantly reduces basal ion transport across H441 monolayers by about 50% compared to controls (measured as short circuit current). AICAR and phenformin both significantly lower amiloride-sensitive transepithelial Na+ transport than controls. Through the activation of AMPK and the inhibition of apical Na+ entry through ENaC and basolateral Na+ extrusion through the Na+,K+-ATPase, phenformin and AICAR inhibit amiloride-sensitive Na+ transport across H441 cells.[4] A tendency for a drop in blood insulin levels is seen in phenformin-treated rats (radioimmunoassay).[5]
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ln Vivo |
Phenformin also increases levels of P-eIF2α and its target BiP/Grp78 in normal lung as well as in lung tumors of mice.[3]
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Enzyme Assay |
Total AMPK activity is measured using the method of Dagher et al. AMPK activity is quantified in the resuspended pellet as incorporation of32P from [γ-32P]ATP (10 GBq/mmol) into a synthetic peptide with the specific target sequence for AMPK, the SAMS peptide. Radioactivity is measured using a liquid scintillation counter. Protein content in the solution containing the resupended (NH4)2SO4pellet is determined using the Bradford method.
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Cell Assay |
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).
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Animal Protocol |
Mice;
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References |
Molecular Formula |
C10H15N5
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Molecular Weight |
205.2596
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Elemental Analysis |
C, 49.69; H, 6.67; Cl, 14.67; N, 28.97
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CAS # |
834-28-6
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Related CAS # |
Phenformin;114-86-3;Phenformin-d5 hydrochloride
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Appearance |
Solid powder
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SMILES |
C1=CC=C(C=C1)CCN=C(N)N=C(N)N.Cl
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InChi Key |
YSUCWSWKRIOILX-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C10H15N5.ClH/c11-9(12)15-10(13)14-7-6-8-4-2-1-3-5-8;/h1-5H,6-7H2,(H6,11,12,13,14,15);1H
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Chemical Name |
1-(diaminomethylidene)-2-(2-phenylethyl)guanidine;hydrochloride
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Synonyms |
W-104144; ST-50409947; D-08352; W104144; ST50409947; D08352; W 104144; ST 50409947; D 08352; Phenformin Hydrochloride; Phenformin HCl; Meltrol; Dipar; Phenethylbiguanide hydrochloride;
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HS Tariff Code |
2934.99.9001
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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)
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Solubility (In Vitro) |
DMSO: ~48 mg/mL (~198.6 mM)
Water: ~48 mg/mL (~198.6 mM) Ethanol: ~12 mg/mL (~49.6 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.42 mg/mL (1.74 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 4.2 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: ≥ 0.42 mg/mL (1.74 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 4.2 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. View More
Solubility in Formulation 3: ≥ 0.42 mg/mL (1.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 2.5 mg/mL (10.34 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 4.8719 mL | 24.3593 mL | 48.7187 mL | |
5 mM | 0.9744 mL | 4.8719 mL | 9.7437 mL | |
10 mM | 0.4872 mL | 2.4359 mL | 4.8719 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.