N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐用途

W-7 hydrochloride 是一种选择性的钙调蛋白 (calmodulin) 拮抗剂。W-7 hydrochloride 抑制 Ca2+-钙调蛋白依赖性磷酸二酯酶 (phosphodiesterase) 和肌球蛋白轻链激酶 (myosin light chain kinase),IC50 值分别为 28 μM 和 51 μM。W-7 hydrochloride 可诱导细胞凋亡 (apoptosis),并具有抗癌活性。

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N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐名称

[ CAS 号 ]:
61714-27-0

[ 中文名 ]:
N-(6-氨基己基)-5-氯-1-萘磺胺盐酸盐

[ 英文名 ]:
W-7 hydrochloride

[中文别名 ]:

[英文别名 ]:

W-7
W-7 HYDROCHLORIDE
MFCD00012559
L66J BSWM6Z GG &&HCl

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

信号通路 >> 神经信号通路 >> 蛋白激酶

信号通路 >> 代谢酶/蛋白酶 >> 磷酸二酯酶(PDE)

信号通路 >> 细胞骨架 >> 肌球蛋白

[ 靶点 ]

IC50: 28 μM (Phosphodiesterase) and 51 µM (Myosin light chain kinase)[1]

[体外研究]

W-7主要分布于细胞质中,对中国仓鼠卵巢K1细胞增殖有抑制作用。W-7选择性地阻断细胞周期(G1/S边界相)。25μM W-7在细胞周期G1/S边界期阻止细胞生长[1]。W-7(100μM)对卡巴胆碱和KCl的收缩反应有相似程度的拮抗作用。W-7可抑制10μM卡巴胆碱刺激1min后肌球蛋白轻链磷酸含量的增加。W-7通过抑制P-LC磷酸化的初始增加而拮抗平滑肌收缩[2]。W-7治疗可导致不同人类多发性骨髓瘤细胞系的细胞增殖受到剂量依赖性抑制。W-7通过下调细胞周期蛋白和上调p21cip1诱导G1期细胞周期阻滞。W-7通过caspase激活诱导细胞凋亡；这部分通过细胞内钙水平的升高和线粒体膜电位的去极化,以及通过抑制STAT3磷酸化和随后Mcl-1蛋白的下调来实现[3]。W-7竞争性抑制Ca2+/钙调蛋白依赖性磷酸二酯酶,Ki值为300μM[4]。

[体内研究]

W-7(3mg/kg；腹腔注射；每周连续5天；雌性BALB/c nu小鼠)治疗显著降低小鼠MM模型中的肿瘤生长[3]。动物模型：雌性BALB/c nu小鼠(6周龄)注射RPMI 8226细胞[3]剂量：3mg/kg给药：腹腔注射；每周连续5天结果：小鼠MM模型中肿瘤生长明显减少。

[参考文献]

[1]. H Hidaka, et al. N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a Calmodulin Antagonist, Inhibits Cell Proliferation. Proc Natl Acad Sci U S A. 1981 Jul;78(7):4354-7.

[2]. M Asano. Divergent Pharmacological Effects of Three Calmodulin Antagonists, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), Chlorpromazine and Calmidazolium, on Isometric Tension Development and Myosin Light Chain Phosphorylation in Intact Bovine Tracheal Smooth Muscle. J Pharmacol Exp Ther. 1989 Nov;251(2):764-73.

[3]. H Itoh, et al. Direct Interaction of Calmodulin Antagonists With Ca2+/calmodulin-dependent Cyclic Nucleotide Phosphodiesterase. J Biochem. 1984 Dec;96(6):1721-6.

[4]. Shigeyuki Yokokura, et al. Calmodulin Antagonists Induce Cell Cycle Arrest and Apoptosis in Vitro and Inhibit Tumor Growth in Vivo in Human Multiple Myeloma. BMC Cancer. 2014 Nov 26;14:882.

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐物理化学性质

[ 沸点 ]:
518.8ºC at 760 mmHg

[ 熔点 ]:
220-222 °C

[ 分子式 ]:
C₁₆H₂₂Cl₂N₂O₂S

[ 分子量 ]:
377.329

[ 闪点 ]:
267.6ºC

[ 精确质量 ]:
376.077911

[ PSA ]:
80.57000

[ LogP ]:
6.26460

[ 储存条件 ]:
−20°C

[ 水溶解性 ]:
methanol: 25 mg/mL, clear, colorless

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐MSDS

详细MSDS(安全技术说明书)

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐安全信息

[ 个人防护装备 ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ 危害码 (欧洲) ]:
Xi

[ 安全声明 (欧洲) ]:
S22-S24/25

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ RTECS号 ]:
QK0786000

N-(6-氨基己基)-5-氯-1-萘磺酰胺盐酸盐文献

Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum.

Nat. Chem. Biol. 5 , 765-71, (2009)

Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened...

Calmodulin antagonists induce cell cycle arrest and apoptosis in vitro and inhibit tumor growth in vivo in human multiple myeloma.

BMC Cancer 14 , 882, (2014)

Human multiple myeloma (MM) is an incurable hematological malignancy for which novel therapeutic agents are needed. Calmodulin (CaM) antagonists have been reported to induce apoptosis and inhibit tumo...

Calmodulin and PI(3,4,5)P₃ cooperatively bind to the Itk pleckstrin homology domain to promote efficient calcium signaling and IL-17A production.

Sci. Signal. 7(337) , ra74, (2014)

Precise regulation of the kinetics and magnitude of Ca(2+) signaling enables this signal to mediate diverse responses, such as cell migration, differentiation, vesicular trafficking, and cell death. W...

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