Phenformin HCl
(Synonyms: 盐酸苯乙福明; Phenethylbiguanide hydrochloride) 目录号 : GC10461
An antihyperglycemic biguanide
Cas No.:834-28-6
Sample solution is provided at 25 µL, 10mM.
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Phenformin hydrochloride is an anti-diabetic drug from the biguanide class, can activate AMPK activity.
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 eIF2α 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].
Phenformin increases levels of P-eIF2α and its target BiP/Grp78 in normal lung as well as in lung tumors of mice[3].
References:
[1]. Sakamoto K, et al. Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR. Am J Physiol Endocrinol Metab. 2004 Aug;287(2):E310-7.
[2]. Zhang L, et al. Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H457-66.
[3]. Moreira AL, et al. Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation. J Exp Med. 1993 Jun 1;177(6):1675-80.
[4]. Woollhead AM, et al. Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells. J Physiol. 2005 Aug 1;566(Pt 3):781-92. Epub 2005
[5]. Dilman VM, et al. Inhibition of DMBA-induced carcinogenesis by phenformin in the mammary gland of rats. Arch Geschwulstforsch. 1978;48(1):1-8.
| Cell experiment [1]: | |
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Cell lines |
BRAFV600E Me-1 melanoma cells and HEK-293 cells |
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Preparation method |
The solubility of this compound in DMSO is > 12.1 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
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Reacting condition |
1 or 5 mM; 2 hrs |
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Applications |
In BRAFV600E Me-1 melanoma cell line (with impaired AMPK activation), 1 and 5 mM Phenformin significantly increased AMPK kinase activity, in a dose-dependent manner. A similar increase was also observed in HEK-293 cells (as control cells). These results implied that the presence of BRAFV600E in melanoma cells did not prevent the pharmacological activation of AMPK, and that AMPK was activated by the increase in phosphorylation of a key AMPK downstream target (ACC). |
| Animal experiment [2]: | |
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Animal models |
Tyr::CreER; BRAFCA/+; PTENlox/lox mice bearing single tumor induced by 4-HT |
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Dosage form |
100 mg/kg; p.o.; b.i.d. |
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Applications |
In Tyr::CreER; BRAFCA/+; PTENlox/lox mice bearing single tumor induced by 4-HT, the combination of Phenformin and PLX4720 significantly inhibited tumor growth. PLX4720 alone substantially reduced the rate of tumor progression, but Phenformin alone only showed a modest inhibition on tumor growth in these mice. According to immunohistochemical analyses of these tumors, the Phenformin/PLX4720 combination dramatically promoted apoptotic cell death and inhibited tumor cell proliferation. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Petti C, Vegetti C, Molla A, Bersani I, Cleris L, Mustard KJ, Formelli F, Hardie GD, Sensi M, Anichini A. AMPK activators inhibit the proliferation of human melanomas bearing the activated MAPK pathway. Melanoma Res. 2012 Oct;22(5):341-50. [2]. Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, Bosenberg MW, McMahon M, Cantley LC, Zheng B. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18226-31. |
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| Cas No. | 834-28-6 | SDF | |
| 别名 | 盐酸苯乙福明; Phenethylbiguanide hydrochloride | ||
| 化学名 | 1-(diaminomethylidene)-2-(2-phenylethyl)guanidine;hydrochloride | ||
| Canonical SMILES | C1=CC=C(C=C1)CCN=C(N)N=C(N)N.Cl | ||
| 分子式 | C10H16ClN5 | 分子量 | 241.72 |
| 溶解度 | ≥ 12.1mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.137 mL | 20.6851 mL | 41.3702 mL |
| 5 mM | 0.8274 mL | 4.137 mL | 8.274 mL |
| 10 mM | 0.4137 mL | 2.0685 mL | 4.137 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet