Phenamil methanesulfonate

Phenamil methanesulfonate用途

Phenamil methanesulfonate 是 Amiloride (HY-B0285) 的类似物,一种更有效且不可逆的上皮钠通道 (ENaC) 阻滞剂,IC50 为 400 nM。Phenamil methanesulfonate 也是 TRPP3 的竞争性抑制剂,在 Ca2+ 摄取实验中,抑制 TRPP3 介导的 Ca2+ 转运的 IC50 为 140 nM。Phenamil methanesulfonate 是一种通过强烈激活 BMP 信号通路来促进骨修复的小分子。Phenamil methanesulfonate 用于囊性纤维化肺疾病的相关研究。

Phenamil methanesulfonate名称

[ CAS 号 ]:
1161-94-0

[ 英文名 ]:
Phenamil methanesulfonate

[英文别名 ]:

Phenaethylphosphorodichloridat
MFCD00274070
2-Cl-IB-MECA
Phenamil methanesulfonate salt
Phosphorodichloridic acid,2-phenylethyl ester

Phenamil methanesulfonate生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钠通道

信号通路 >> 跨膜转运 >> TRP频道

研究领域 >> 炎症/免疫

研究领域 >> 代谢疾病

[ 靶点 ]

TRPC3:140 nM (IC50)

[体外研究]

TRPP3是阳离子通道瞬时受体电位(TRP)超家族成员之一,是一种钙离子激活的通道,对Ca2+、Na+和K+具有通透性。TRPP3参与脊髓神经元pH敏感动作电位的调节。在放射性示踪剂摄取试验中,甲磺酸酚胺(1μM)可减少45Ca2+的摄取。在表达TRPP3或H2O的卵母细胞中,抑制TRPP3介导的Ca2+转运,IC50值为0.28μM[1]。甲磺酸酚胺是比阿米洛利更有效的ENaC阻滞剂,它抑制上皮钠通道(ENaC),其IC50为400 nM(阿米洛利=776 nM)[2]。甲磺酸芬那米可抑制人和羊支气管上皮细胞的基础短路电流,其IC50值分别为75和116nm[3]。苯那咪尔甲磺酸钠(0-20μM；14d)以浓度依赖性的方式提高成脂基因表达、PPARγ、Fabp4和脂蛋白脂酶的表达,并调节C3H10T1/2细胞的脂肪生成[4]。甲磺酸酚胺(0-20μM；7或14天)调节MC3T3-E1成骨细胞分化,以浓度依赖的方式增加MC3T3-E1细胞碱性磷酸酶(ALP)活性[4]。RT-PCR[4]细胞株：C3H10T1/2细胞浓度：0μM,20μM孵育时间：14d。结果：PPARγ、Fabp4和脂蛋白脂酶(LPL)mRNA表达增加。

[体内研究]

甲磺酸酚胺(皮下注射；15或30mg/kg；21天；输注速率为1ml/h)可降低慢性缺氧性肺动脉高压(PAH)。此外,在缺氧或常氧状态下,非那米可降低肺组织中SMA、SM22、Id3和Trb3的mRNA水平。然而,在生理条件下,非那米尔对肺血管系统影响不大[5]。动物模型：雄性Sprague-Dawley大鼠[5]剂量：15或30mg/kg给药：皮下注射；15或30mg/kg；21天；输注速率为1ml/h。结果：缺氧引起的肺动脉高压和血管重构减轻

[参考文献]

[1]. Xiao-Qing Dai , et al. Inhibition of TRPP3 channel by amiloride and analogs. Mol Pharmacol. . 2007 Dec;72(6):1576-85.

[2]. Andrew J Hirsh, et al.Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis. J Med Chem. 2006 Jul 13;49(14):4098-115.

[3]. Andrew J Hirsh, et al.Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease.J Pharmacol Exp Ther. 2004 Dec;311(3):929-38.

[4]. Mun Chun Chan, et al. The amiloride derivative phenamil attenuates pulmonary vascular remodeling by activating NFAT and the bone morphogenetic protein signaling pathway. Mol Cell Biol

Phenamil methanesulfonate物理化学性质

[ 沸点 ]:
621.7ºC at 760 mmHg

[ 分子式 ]:
C₁₃H₁₆ClN₇O₄S

[ 分子量 ]:
401.829

[ 闪点 ]:
329.8ºC

[ 精确质量 ]:
401.067291

[ PSA ]:
205.55000

[ LogP ]:
3.38190

[ 外观性状 ]:
黄色固体

[ 蒸汽压 ]:
2.22E-15mmHg at 25°C

[ 储存条件 ]:
-20°C

Phenamil methanesulfonateMSDS

详细MSDS(安全技术说明书)

Phenamil methanesulfonate安全信息

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

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

[ 海关编码 ]:
2924299090

Phenamil methanesulfonate海关

[ 海关编码 ]: 2924299090

[ 中文概述 ]:
2924299090. 其他环酰胺（包括环氨基甲酸酯）（包括其衍生物以及他们的盐）. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 包装

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Phenamil methanesulfonate文献

The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning.

Proc. Natl. Acad. Sci. U. S. A. 91 , 247, (1994)

Water balance in the lung is controlled via active Na+ and Cl- transport. Electrophysiological measurements on lung epithelial cells demonstrated the presence of a Na+ channel that is inhibited by ami...

Phenamil: an irreversible inhibitor of sodium channels in the toad urinary bladder.

J. Membr. Biol. 87 , 45, (1985)

Several new amiloride analogues and two reported photoaffinity analogues were tested for irreversible inhibition of short-circuit current, Isc, in toad bladder. Bromoamiloride, a photoaffinity analogu...

Biochemical identification of two types of phenamil binding sites associated with amiloride-sensitive Na+ channels.

Biochemistry 28 , 3744, (1989)

The existence of distinct forms of the epithelium Na+ channel that differ in their sensitivity to amiloride has been repeatedly suggested by physiological data. The biochemical basis for these differe...

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