丁双胍盐酸盐

Buformin hydrochloride (1-Butylbiguanide hydrochloride) 是一种有效的,具有口服活性的降血糖试剂 (antidiabetic agent),是一种 AMPK 活化剂。Buformin 降低肝糖异生并降低血糖生成。Buformin 也具有抗癌活性,可以应用于癌症研究,如宫颈癌、乳腺癌等。

信号通路 >> 表观遗传学 >> AMPK

研究领域 >> 癌症

信号通路 >> PI3K/Akt/mTOR 信号通路 >> AMPK

盐酸二甲双胍(0-10 mM；5天)以浓度依赖的方式抑制SKBR3和BT474细胞生长,对erbB-2过度表达的SKBR3和BT474细胞的IC50值分别为246.7μM和 98.6μM[1]。盐酸二甲双胍(0-3mm；48h)增加G0/G1期细胞百分率,降低S期细胞百分率,尤其是SKBR3细胞[1]。盐酸二甲双胍(0-3 mM；24小时)抑制RTK激活,包括下游的erbB-2和IGF1R信号传导,并且SKBR3和BT474细胞中的Akt激活/磷酸化受到抑制[1]。细胞活力测定[1]细胞系：ErbB-2-过度表达SKBR3和BT474细胞浓度：0μM、1μM、3μM、10μM、30μM、100μM、300μM、1、3或10 mM孵育时间：5天结果：ErbB-2-过度表达乳腺细胞的细胞活力降低。细胞周期分析[1]细胞系：ErbB-2-过度表达的SKBR3和BT474细胞浓度：0.5毫米；1毫米；3毫米孵育时间：48小时结果：细胞数增加,停滞在G0/G1期。Western Blot分析[1]细胞系：ErbB-2-过度表达的SKBR3和BT474细胞浓度：0 mM、0.1 mM、0.3 mM、1 mM或3 mM孵育时间：24小时结果：p-AMPK、p-p706S、p-ERK1/2的表达呈浓度依赖性降低。

盐酸二甲双胍(口服；7.6 mmol/kg chow；7天)在MMTV-erbB-2转基因小鼠中显示出显著减少的肿瘤体积和重量,并阻碍乳腺的形态发生和增殖[1]。动物模型：雌性MMTV-erbB-2转基因小鼠[1]剂量：7.6 mmol/kg给药：口服；7天结果：抑制MMTV-erbB-2转基因小鼠乳腺同基因肿瘤生长。

[1]. Amanda B Parris, et al. 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]. Jing Li, et al. 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.

MOLECULAR FORMULA :

C6-H15-N5.Cl-H

MOLECULAR WEIGHT :

193.72

WISWESSER LINE NOTATION :

MUYZMYUM&M4 &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 :

320 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

380 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 - mouse

DOSE/DURATION :

74 mg/kg

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory stimulation

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

105 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 :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

58 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 :

23 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

MUTATION DATA

TYPE OF TEST :

Cytogenetic analysis

TEST SYSTEM :

Human Embryo

DOSE/DURATION :

1900 ug/L

REFERENCE :

SNSHBT Senshokutai. Chromosome. (Sensyokutai Gakkai, Kaokusai Kirisutokyo Daigaku, Mitaka, Tokyo-to, Japan) No.1- 1946- Adopted new numbering in 1976. Volume(issue)/page/year: (20),574,1980