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氨来呫诺

氨来呫诺用途

AmLexanox 是特异性的 IKKε 和 TBK1 抑制剂,IC50 值为 1-2 μM。

氨来呫诺名称

[ CAS 号 ]:
68302-57-8

[ 中文名 ]:
氨来占诺

[ 英文名 ]:
Amlexanox

[中文别名 ]:

[英文别名 ]:

Amlexanoxum
Amlenanox
Amlexanox
Amlexanoxo
Elics
Amoxanox
Solfa
MFCD00864790
amlexanoxum [INN_la]
Aphthasol

氨来呫诺生物活性

[ 描述 ]:

AmLexanox 是特异性的 IKKε 和 TBK1 抑制剂,IC50 值为 1-2 μM。

[ 相关类别 ]:

信号通路 >> NF-κB信号通路 >> IKK

研究领域 >> 代谢疾病

[ 靶点 ]

IKKε:1-2 μM (IC50)

TBK1:1-2 μM (IC50)

[体外研究]

AmLexanox增加3T3-L1脂肪细胞中Ser172上TBK1的磷酸化,并阻断聚胞苷：聚胞苷酸(poly I：C)刺激的干扰素反应因子-3(IRF3)的磷酸化,这是IKKε和TBK1的假定底物[1]。 AmLexanox在体外环境中有效抑制肥大细胞,嗜碱性粒细胞和中性粒细胞释放组胺和白三烯,可能通过增加炎症细胞内细胞内环AMP含量,降低膜内稳定作用或抑制钙内流[2]。在原代骨髓衍生的巨噬细胞(BMM)中,amLexanox抑制破骨细胞形成和骨吸收。在分子水平上,amLexanox抑制RANKL诱导的核因子-κB(NF-κB),丝裂原活化蛋白激酶(MAPKs),c-Fos和NFATc1的激活。 AmLexanox降低破骨细胞特异性基因的表达,包括TRAP,MMP9,组织蛋白酶K和NFATc1 [3]。

[体内研究]

AmLexanox(100 mg/kg,po)预防和逆转饮食诱导或遗传性肥胖,并在肥胖小鼠中产生可逆的体重减轻。 AmLexanox还导致这些小鼠的脂肪组织质量显着降低,并且循环脂联素增加。 AmLexanox(25 mg/kg)显着改善已建立DIO的小鼠的胰岛素敏感性,治疗4周后,amLexanox可显着改善葡萄糖[1]。 AmLexanox在第一次施用糊剂之前和之后已经显示出抑制立即和之后的评价。分类量表也是迟发型超敏反应[2]。 AmLexanox(20 mg/kg)可增强BMSCs的成骨细胞分化。在卵巢切除(OVX)小鼠模型中,amLexanox通过抑制破骨细胞活性来预防OVX诱导的骨丢失[3]。

[激酶实验]

通过将纯化的激酶（IKKε或TBK1）在含有25mM Tris（pH7.5），10mM MgCl 2,1mM DTT和10μMATP的激酶缓冲液中于30℃温育30分钟来进行体外激酶测定。每个样品存在0.5μCiγ-[32P] -ATP和1μgMBP作为底物。通过加入4x十二烷基硫酸钠（SDS）样品缓冲液并在95℃下煮沸5分钟来终止激酶反应。通过SDS-聚丙烯酰胺凝胶电泳分离上清液，转移至硝酸纤维素，并使用Typhoon 9410磷成像仪通过放射自显影分析。

[细胞实验]

为了检查细胞增殖，根据制造商的说明使用细胞计数试剂盒-8。将BMM以5×10 3个细胞/孔的密度接种在96孔板中。 24小时后，在M-CSF（30ng / mL）存在下，每2天用不同浓度的AmLexanox（0,1.5,3,6,12,25μM）处理细胞7天。在1,3,5和7天后，用含有10％CCK-8的培养基替换培养基，并将细胞在37℃下再培养2小时。然后在ELX800吸光度酶标仪上在450nm波长下测量吸光度。

[动物实验]

向野生型雄性C57BL / 6小鼠喂食HFD，其由来自8周龄的脂肪的45％卡路里组成，持续12-24周，而ND C57BL / 6对照维持在由4.5％脂肪组成的正常食物饲料上。饲喂含有ω-3脂肪酸的C57BL / 6日粮。通过在已经在HFD上持续16周的小鼠中将化合物添加到饮食中来施用罗格列酮治疗三周。每只小鼠平均每天消耗3.5mg / kg罗格列酮。 AmLexanox通过每日口服强饲法给药。对于预防组，amLexanox（25mg / kg或100mg / kg）与8周龄HFD喂养同时开始。对于治疗组，在HFD 12周后，在20周龄时开始每公斤25mg amLexanox治疗。为了测试amLexanox戒断的效果，在amLexanox处理8周后，处理组中的小鼠从amLexanox管饲法转换为载体对照。对照组和ob / ob小鼠用正常饲料喂养，并在10周龄时开始用100mg / kg amLexanox或载体对照饲养。将动物饲养在无特定病原体的设施中，12小时光照/ 12小时黑暗循环，并自由获取食物和水。

[参考文献]

[1]. Reilly SM, et al. An inhibitor of the protein kinases TBK1 and IKK-e improves obesity-related metabolic dysfunctions in mice. Nat Med. 2013 Mar;19(3):313-21.

[2]. Bell, J. AmLexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig, 2005. 25(9): p. 555-66.

[3]. Zhang Y, et al. AmLexanox Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss. Sci Rep. 2015 Sep 4;5:13575.

[相关活性小分子]

氨来呫诺物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
570.0±50.0 °C at 760 mmHg

[ 熔点 ]:
>3000C

[ 分子式 ]:
C₁₆H₁₄N₂O₄

[ 分子量 ]:
298.293

[ 闪点 ]:
298.5±30.1 °C

[ 精确质量 ]:
298.095367

[ PSA ]:
106.42000

[ LogP ]:
3.74

[ 外观性状 ]:
白色结晶固体

[ 蒸汽压 ]:
0.0±1.6 mmHg at 25°C

[ 折射率 ]:
1.669

[ 储存条件 ]:
-20°C Freezer

氨来呫诺MSDS

详细MSDS(安全技术说明书)

氨来呫诺毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DJ3102000

CHEMICAL NAME :: 5H-(1)Benzopyrano(2,3-b)pyridine-3-carboxylic acid, 2-amino-7-(1-methylethyl)-5-oxo-

CAS REGISTRY NUMBER :: 68302-57-8

LAST UPDATED :: 199612

DATA ITEMS CITED :: 9

MOLECULAR FORMULA :: C16-H14-N2-O4

MOLECULAR WEIGHT :: 298.32

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 :: 10 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 500 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1400 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2320 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 450 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3310 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - body temperature decrease

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6405,1985 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 35 gm/kg/5W-I

TOXIC EFFECTS :: Gastrointestinal - other changes Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,4843,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 54600 mg/kg/26W-C

TOXIC EFFECTS :: Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,6411,1985

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 3500 mg/kg/5W-C

TOXIC EFFECTS :: Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 13,7123,1985

氨来呫诺安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 危害码 (欧洲) ]:
Xn,Xi

[ 风险声明 (欧洲) ]:
R22:Harmful if swallowed. R36/37/38:Irritating to eyes, respiratory system and skin .

[ 安全声明 (欧洲) ]:
S26

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

[ WGK德国 ]:
3

[ RTECS号 ]:
XZ3012000

[ 海关编码 ]:
2934999090

氨来呫诺合成路线

详细合成路线

氨来呫诺上下游产品

氨来呫诺上游产品

氨来呫诺下游产品

氨来呫诺制备

3-氰基6-异丙基苯并吡喃酮(I)在含吗啉和二甲基甲酰胺的水溶液中，在60℃加热反应，得到化合物(Ⅱ)。再和丙二酸单乙酯酰胺缩合环合，然后水解得到氨来咕诺。

氨来呫诺海关

[ 海关编码 ]: 2934999090

[ 中文概述 ]:
2934999090. 其他杂环化合物. 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:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

氨来呫诺文献

Hydroxychloroquine-inhibited dengue virus is associated with host defense machinery.

J. Interferon Cytokine Res. 35(3) , 143-56, (2015)

Hydroxychloroquine (HCQ) is an antimalarial drug also used in treating autoimmune diseases. Its antiviral activity was demonstrated in restricting HIV infection in vitro; however, the clinical implica...

Role of G Protein-Coupled Receptor Kinases 2 and 3 in μ-Opioid Receptor Desensitization and Internalization.

Mol. Pharmacol. 88 , 347-56, (2015)

There is ongoing debate about the role of G protein-coupled receptor kinases (GRKs) in agonist-induced desensitization of the μ-opioid receptor (MOPr) in brain neurons. In the present paper, we have u...

Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation.

Nat. Commun. 6 , 6074, (2015)

Development of an immune or autoimmune response involves T-cell activation in lymphoid organs and subsequent migration to peripheral tissues. Here we show that T-cell-specific ablation of the kinase T...

更多文献

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氨来呫诺的作用和生物活性

2018-10-30 14:16:55

氨来呫诺是一种抗口疮性溃疡药物。氨来呫诺抑制肥大细胞，中性粒细胞和单核细胞中炎症介质（包括白三烯和组胺）的合成和释放。氨来呫诺还可作为白三烯D4拮抗剂和磷酸二酯酶抑制剂。氨来呫诺减少溃疡愈合的时间以及与溃疡相关的疼痛。一、氨来呫诺的生物活性详解：1）体外活性氨来呫诺可增加3T3-L1脂肪细胞中Se...