Amlexanox (AA673)
(Synonyms: 氨来呫诺; AA673; Amoxanox; CHX3673) 目录号 : GC31319
Amlexanox (AA673)是一种具有口服活性的三环胺羧酸类化合物，可有效抑制TANK结合激酶1（TBK1）（IC50=0.8μM）和抑制因子κB激酶ε（IKK-ε）（IC50=5.8μM）。
Cas No.:68302-57-8
Sample solution is provided at 25 µL, 10mM.
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Amlexanox (AA673), a tricyclic amine carboxylic acid with oral activity, can effectively inhibit TANK-binding kinase 1 (TBK1) (IC50 = 0.8μM) and inhibitor-kappaB kinase epsilon (IKK-ɛ) (IC50 = 5.8μM)[1]. Amlexanox selectively inhibits G protein-coupled receptor kinase (GRK) 5 (IC50 =8.86μM), which can used as an anti-inflammatory and anti-allergic immunomodulator in various animal models[2].
In vitro, Amlexanox treatment for 72h significantly inhibited the proliferation of U87 cells and U251 cells, with IC50 values of 140μM and 120μM, respectively[3]. The treatment with Amlexanox (6μM) for 24 hours significantly reduced the expression of pro-inflammatory cytokines and chemokines in murine BV2 cells, and human HMC3 microglial cells induced by lipopolysaccharide (LPS) (100ng/ml)[4]. Treatment of PC3 cells with 5μM Amlexanox for 7 days resulted in upregulation of adhesion molecules (EpCAM, DSP, Claudin1, ZO1 and E-cadherin), and inhibition of mesenchymal genes and integrin α5[5].
In vivo, Amlexanox treatment via daily oral administration at a dose of 25mg/kg for 8 weeks prevented and reversed obesity caused by a high-fat diet in male C57BL/6 mice [6]. Treatment of Amlexanox (50mg/kg/day; p.o.)for 4 weeks decreased hepatic fibrogenic responses in mice with biliary fibrosis and accelerated fibrosis resolution[7]. Oral administration of Amlexanox (50mg/kg) twice daily for 30 days significantly reduced inflammatory infiltration and demyelination in the spinal cord tissue of the experimental autoimmune encephalomyelitis mouse model, and prevented weight loss in the mice[8].
References:
[1] Bailly C. The potential value of amlexanox in the treatment of cancer: Molecular targets and therapeutic perspectives[J]. Biochemical Pharmacology, 2022, 197: 114895.
[2] Zhang Y, Zhang J, Wang J, et al. Targeting GRK2 and GRK5 for treating chronic degenerative diseases: Advances and future perspectives[J]. European Journal of Medicinal Chemistry, 2022, 243: 114668.
[3] Liu Y, Lu J, Zhang Z, et al. Amlexanox, a selective inhibitor of IKBKE, generates anti-tumoral effects by disrupting the Hippo pathway in human glioblastoma cell lines[J]. Cell death & disease, 2017, 8(8): e3022-e3022.
[4] Phan Van T, Huyen Ton Nu Bao T, Leya M, et al. Amlexanox attenuates LPS-induced neuroinflammatory responses in microglial cells via inhibition of NF–κB and STAT3 signaling pathways[J]. Scientific Reports, 2024, 14(1): 2744.
[5] Cheng C, Ji Z, Sheng Y, et al. Aphthous ulcer drug inhibits prostate tumor metastasis by targeting IKKɛ/TBK1/NF-κB signaling[J]. Theranostics, 2018, 8(17): 4633.
[6] Reilly S M, Chiang S H, Decker S J, et al. An inhibitor of the protein kinases TBK1 and IKK-ɛ improves obesity-related metabolic dysfunctions in mice[J]. Nature medicine, 2013, 19(3): 313-321.
[7] Zhou Z, Qi J, Zhao J, et al. Dual TBK1/IKKɛ inhibitor amlexanox attenuates the severity of hepatotoxin‐induced liver fibrosis and biliary fibrosis in mice[J]. Journal of Cellular and Molecular Medicine, 2020, 24(2): 1383-1398.
[8] Quan M Y, Song X J, Liu H J, et al. Amlexanox attenuates experimental autoimmune encephalomyelitis by inhibiting dendritic cell maturation and reprogramming effector and regulatory T cell responses[J]. Journal of neuroinflammation, 2019, 16(1): 52.
Amlexanox (AA673)是一种具有口服活性的三环胺羧酸类化合物，可有效抑制TANK结合激酶1（TBK1）（IC50=0.8μM）和抑制因子κB激酶ε（IKK-ε）（IC50=5.8μM）[1]。Amlexanox选择性抑制G蛋白偶联受体激酶（GRK）5（IC50=8.86μM），在多种动物模型中作为抗炎和抗过敏免疫调节剂 [2]。
在体外，Amlexanox处理72小时可显著抑制U87和U251细胞增殖，IC50值分别为140μM和120μM[3]。6μM的Amlexanox处理24小时能显著降低脂多糖（LPS）(100ng/ml）诱导的小鼠BV2细胞和人HMC3小胶质细胞中促炎细胞因子和趋化因子表达[4]。5μM的Amlexanox处理PC3细胞7天可上调黏附分子（EpCAM、DSP、Claudin1、ZO1和E-钙黏蛋白）表达，并抑制间充质基因和整合素α5[5]。
在体内，雄性C57BL/6小鼠每日口服Amlexanox（25mg/kg；持续8周）可预防和逆转高脂饮食诱导的肥胖[6]。胆道纤维化小鼠每日口服50mg/kg剂量的Amlexanox（持续4周）能减轻肝纤维化反应并加速纤维化消退[7]。实验性自身免疫性脑脊髓炎小鼠模型每日两次口服50mg/kg剂量的Amlexanox（持续30天）可显著减少脊髓组织炎症浸润和脱髓鞘，并防止体重下降[8]。
| Cell experiment [1]: | |
Cell lines | U87 cells |
Preparation Method | U87 cells were cultured in the Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% fetal bovine serum (FBS), and were maintained in a humidified environment at 37°C and 5% CO2. U87 cells (4 × 103 cells per well) were seeded in a 96-well plate and incubated for 12 hours. Then, the cells were treated with different concentrations of Amlexanox (6.25, 12.5, 25, 50, 100, 200, 250, and 300µM). After incubation with Amlexanox for 24, 48, 72 or 96 hours, CCK-8 was added to each well and the cells were incubated for 1.5 hours. The optical density at 450nm was measured using a microplate reader. |
Reaction Conditions | 6.25, 12.5, 25, 50, 100, 200, 250, and 300µM; 24, 48, 72, and 96h |
Applications | Amlexanox treatment significantly inhibited cell viability of U87 cells in a dose- and time-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female C57BL/6 mice |
Preparation Method | Female C57BL/6 mice (6-8 weeks old, 18-20g) were housed in a specific pathogen-free animal room with a 12-hour day-night cycle, with free access to food and water. The mice were immunized subcutaneously on the back with the oligomeric glycoprotein peptide of myelin oligodendrocyte glycoprotein (MOG35-55, 250μg per mouse) in 50% complete Freund's adjuvant (CFA), which contained 4mg/ml heat-inactivated Mycobacterium tuberculosis H37Ra. On days 0 and 2, the mice were intraperitoneally injected with pertussis toxin (500ng per mouse). The mice were randomly grouped, and from the day of immunization, they were orally administered the vehicle or Amlexanox twice daily at a dose of 50mg/kg. From the day of immunization until day 29, the mice were weighed and examined daily, and the severity of the disease was analyzed. |
Dosage form | 50mg/kg twice daily for 30 days; p.o. |
Applications | Amlexanox treatment reduced inflammatory infiltration and demyelination in the spinal cord tissue of mice, alleviating the severity of experimental autoimmune encephalomyelitis and preventing weight loss in mice. |
References: | |
| Cas No. | 68302-57-8 | SDF | |
| 别名 | 氨来呫诺; AA673; Amoxanox; CHX3673 | ||
| Canonical SMILES | O=C(C1=C(N)N=C2C(C(C3=CC(C(C)C)=CC=C3O2)=O)=C1)O | ||
| 分子式 | C16H14N2O4 | 分子量 | 298.29 |
| 溶解度 | DMSO : ≥ 36 mg/mL (120.69 mM) | 储存条件 | Store at RT |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3524 mL | 16.7622 mL | 33.5244 mL |
| 5 mM | 0.6705 mL | 3.3524 mL | 6.7049 mL |
| 10 mM | 0.3352 mL | 1.6762 mL | 3.3524 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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