834-28-6

• 常用中文名：盐酸苯乙双胍
• 常用英文名：Phenformin (hydrochloride)
• CAS号：834-28-6
• 分子式：C₁₀H₁₆ClN₅
• 分子量：241.721
• 相关类别： 原料药 激素及调节内分泌功能类药 胰腺激素及其它调节血糖药
• 发布时间：2018-03-10 08:00:00
• 更新时间：2024-01-02 17:18:12
• Phenformin hydrochloride 是一种双胍类的抗糖尿病药,能够使 AMPK 活化。

名称

• 中文名: 盐酸苯乙福明
• 英文名: Phenformin hydrochloride
• 中文别名: 苯乙双胍盐酸盐; 降糖灵; 苯乙双胍盐酸盐; 盐酸苯乙双胍; 盐酸苯乙双胍; 1-(2-苯乙基)双胍盐酸盐; 酸苯乙双胍
• 英文别名: Phenformin hydrochloride; Phenformini Hydrochloride; Insora; meltrol; phenforminhclno.9113; Imidodicarbonimidic diamide, N-(2-phenylethyl)-, hydrochloride (1:1); Glucopostin; Phenformine HCL; dbi-td; β-PEBG HCl; DBI monohydrochloride; usafvi-6; MFCD00035039; Phenformin HCl; PhenforMin HCl API; UNII-91XC93EU03; EINECS 212-637-3; Insoral; N-(2-Phenylethyl)imidodicarbonimidic diamide hydrochloride (1:1); N-Phenethylbiguanide hydrochloride; 1-(2-Phenylethyl)biguanide hydrochloride; N'-b-Phenethylformamidinyliminourea Hydrochloride; Phenformin (hydrochloride); 1,1-Benzylmethylbiguanide hydrochloride

物化性质

• 密度: 1.24 g/cm3
• 沸点: 413.7ºC at 760 mmHg
• 熔点: 175-178ºC
• 分子式: C₁₀H₁₆ClN₅
• 分子量: 241.721
• 闪点: 204ºC
• 精确质量: 241.109421
• PSA: 97.78000
• LogP: 2.72010
• 外观性状: 白色粉末
• 储存条件: -20°C Freezer
• 水溶解性: >=10 g/100 mL at 21 ºC

生物活性

• 描述: Phenformin hydrochloride 是一种双胍类的抗糖尿病药,能够使 AMPK 活化。
• 相关类别:
  信号通路 >> 表观遗传学 >> AMPK
  信号通路 >> PI3K/Akt/mTOR 信号通路 >> AMPK
  研究领域 >> 癌症
• 靶点:

  AMPK

• 体外研究: 苯乙双胍刺激AMPKalpha1和AMPKalpha2的磷酸化和活化而不改变LKB1活性[1]。苯乙双胍增加分离心脏的AMPK活性和磷酸化,AMPK活性的增加总是先于细胞溶质[AMP]增加并与其相关[2]。苯乙双胍是一种比二甲双胍更有效的线粒体复合物I抑制剂50倍。苯乙双胍在LKB1缺陷的NSCLC细胞系中强烈诱导细胞凋亡。 2mM的苯乙双胍类似地诱导AMPK信号传导,如P-AMPK和P-Raptor水平增加所示。苯乙双胍诱导较高水平的细胞应激,引发P-Ser51eIF2α及其下游靶CHOP的诱导,以及后期细胞凋亡的标志物。在长期治疗后,苯乙双胍诱导KLluc小鼠的存活率和治疗反应显着增加[3]。苯乙双胍和AICAR以剂量依赖的方式增加H441细胞中的AMPK活性,分别在5-10mm和2mm处刺激激酶。与对照组相比,苯乙双胍显着降低H441单层的基础离子转运(以短路电流测量)约50％。与对照相比,苯乙双胍和AICAR显着降低阿米洛利敏感的跨上皮Na +转运。苯乙双胍和AICAR通过一种途径抑制阿米洛利敏感的Na +转运穿过H441细胞,该途径包括激活AMPK和通过ENaC抑制顶端Na +进入和通过Na +,K + -ATP酶抑制基底外Na +挤压[4]。苯乙双胍治疗的大鼠显示出血胰岛素水平降低的趋势(放射免疫测定)[5]。
• 体内研究: 苯乙双胍增加正常肺以及小鼠肺肿瘤中P-eIF2α及其靶BiP/Grp78的水平[3]。
• 激酶实验: 使用Dagher等人的方法测量总AMPK活性。在重悬的沉淀中定量AMPK活性，如将来自[γ-32P] ATP（10GBq / mmol）的32P掺入具有AMPK特异性靶序列SAMS肽的合成肽中。使用液体闪烁计数器测量放射性。使用Bradford方法测定含有重悬的（NH 4）2 SO 4沉淀的溶液中的蛋白质含量。
• 参考文献:

  [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.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : DU2200000 CHEMICAL NAME : Biguanide, 1-phenethyl-, monohydrochloride CAS REGISTRY NUMBER : 834-28-6 LAST UPDATED : 199706 DATA ITEMS CITED : 10 MOLECULAR FORMULA : C10-H15-N5.Cl-H MOLECULAR WEIGHT : 241.76 WISWESSER LINE NOTATION : MUYZMYUM&M2R &GH HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 938 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 140 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 17500 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - cyanosis Lungs, Thorax, or Respiration - respiratory depression TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 407 mg/kg TOXIC EFFECTS : Endocrine - hypoglycemia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 150 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 200 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 17800 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 47 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - guinea pig DOSE/DURATION : 19 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value MUTATION DATA TYPE OF TEST : DNA damage TEST SYSTEM : Rodent - rat Liver DOSE/DURATION : 1 mmol/L REFERENCE : EMMUEG Environmental and Molecular Mutagenesis. (Alan R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.10- 1987- Volume(issue)/page/year: 24,181,1994

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302
• 个人防护装备: dust mask type N95 (US);Eyeshields;Gloves
• 危害码 (欧洲): Xn:Harmful
• 风险声明 (欧洲): R22
• 安全声明 (欧洲): S36
• 危险品运输编码: 2811.0
• WGK德国: 3
• RTECS号: DU2200000
• 危险类别: 6.1
• 海关编码: 2942000000

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