BAM 15
目录号 : GC19056
BAM15是一种新型线粒体质子解耦解偶联剂(2-氟苯基){6-(1,2,5-恶二唑啉吡嗪-5-基)}胺,不去极化质膜。
Cas No.:210302-17-3
Sample solution is provided at 25 µL, 10mM.
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BAM15 is a novel mitochondrial protonophore uncoupler (2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine, that does not depolarize the plasma membrane[1].
BAM15 has an average EC50 value of 1.4 µM and is capable of maintaining high levels of mitochondrial respiration over a wide concentration range of 3 to 100 µM in OCR[2]. In fully differentiated C2C12 mouse myotubes, BAM15 (100 µM;16h) did not alter cell viability or number,but BAM15 improves cellular respiratory kinetics by sustained mitochondrial uncoupling[3]. Wild-type animals treated with both 50 µM BAM15 showed reduced mechanosensory neuronal defects during aging, which correlates with the maintenance of touch responses and short-term memory during aging in Caenorhabditis elegans[4]. BAM15(1mM) depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells[5].
BAM15(1 mg/kg; i.p.; 3 hours before injection of LPS) attenuated serum cytokines, organ damage (liver enzymes and serum creatinine) and tissue cytokines (liver and kidney), and reduced inflammatory mononuclear/macrophages in the liver, in part by enhancing phosphorylated αAMPK in LPS-administered mice[6]. BAM15 was seen to reduce mortality after injection at 0, 6 and 12 hours after cecal ligation and puncture (CLP), and reduced kidney damage and spleen apoptosis even after 12 hours when the mice were sick[7].
References:
[1]. Kenwood BM, Weaver JL, et,al. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab. 2013 Nov 28;3(2):114-23. doi: 10.1016/j.molmet.2013.11.005. PMID: 24634817; PMCID: PMC3953706.
[2]. Alexopoulos SJ, Chen SY, et,al. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice. Nat Commun. 2020 May 14;11(1):2397. doi: 10.1038/s41467-020-16298-2. PMID: 32409697; PMCID: PMC7224297.
[3]. Axelrod CL, King WT, et,al. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med. 2020 Jul 7;12(7):e12088. doi: 10.15252/emmm.202012088. Epub 2020 Jun 10. PMID: 32519812; PMCID: PMC7338798.
[4]. Cho I, Song HO, et,al. BAM15 Relieves Neurodegeneration in Aged Caenorhabditis elegans and Extends Lifespan. Metabolites. 2022 Nov 17;12(11):1129. doi: 10.3390/metabo12111129. PMID: 36422268; PMCID: PMC9698188.
[5]. Tai Y, Li L, et,al. Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells. Acta Pharm Sin B. 2018 Oct;8(6):909-918. doi: 10.1016/j.apsb.2018.07.010. Epub 2018 Jul 26. PMID: 30505660; PMCID: PMC6251816.
[6]. Dang CP, Issara-Amphorn J, et,al. BAM15, a Mitochondrial Uncoupling Agent, Attenuates Inflammation in the LPS Injection Mouse Model: An Adjunctive Anti-Inflammation on Macrophages and Hepatocytes. J Innate Immun. 2021;13(6):359-375. doi: 10.1159/000516348. Epub 2021 Jun 1. PMID: 34062536; PMCID: PMC8613553.
[7]. Tsuji N, Tsuji T, et,al. BAM15 treats mouse sepsis and kidney injury, linking mortality, mitochondrial DNA, tubule damage, and neutrophils. J Clin Invest. 2023 Feb 9:e152401. doi: 10.1172/JCI152401. Epub ahead of print. PMID: 36757801.
BAM15是一种新型线粒体质子解耦解偶联剂(2-氟苯基){6-[(2-氟苯基)氨基](1,2,5-恶二唑啉[3,4-e]吡嗪-5-基)}胺,不去极化质膜[1]。
BAM15在刺激耗氧率(OCR)方面展现出了强大的能力,BAM15平均EC50值为1.4 µM,并且能够在3 ~ 100 µM的大浓度范围内维持高水平的线粒体呼吸[2]。在完全分化的C2C12小鼠肌管中,BAM15 (100 µM;16h)不改变细胞活力或数量,但会通过持续的线粒体解耦改善细胞呼吸动力学[3]。用50 µM BAM15处理的野生型秀丽隐杆线虫在衰老过程中表现出机械感觉神经元缺陷的减少,这与衰老过程中触摸反应和短期记忆的维持有关[4]。BAM15能有效激活A10细胞中的AMPK,且BAM15的作用强于CCCP、氯硝柳胺、AMPK阳性激活剂二甲双胍和AICAR[5]。
BAM15在一定程度上通过增强磷酸化的αAMPK减弱了肝脏中的血清细胞因子,器官损伤(肝酶和血清肌酐)和组织细胞因子(肝脏和肾脏),并减少了肝脏中的炎性单核/巨噬细胞[6]。BAM15在盲肠结扎和穿刺(CLP)后0,6和12小时注射后降低死亡率,即使在小鼠生病12小时后也能减少肾脏损伤和脾凋亡[7]。
| Cell experiment [1]: | |
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Cell lines |
Normal murine liver (NMuLi) cells |
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Preparation Method |
NMuLi cells were seeded in a 96-well seahorse plates and were allowed to adhere overnight. Prior to the assay, media was changed to unbuffered DMEM containing pyruvate and glutamine and the cells were equilibrated for 1 h at 37℃ without CO2. BAM15 were injected during the assay and OCR(Oxygen consumption rate) was measured using 2 min measurement periods. |
|
Reaction Conditions |
0.1-100 µM |
|
Applications |
BAM15 has an average EC50 value of 1.4 µM and is capable of maintaining high levels of mitochondrial respiration over a wide concentration range of 3 to 100 µM in OCR. |
| Animal experiment [2]: | |
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Animal models |
Male 6-week-old mice |
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Preparation Method |
BAM15 at 1 mg/kg in 10% of DMSO or 10% DMSO alone was intraperitoneally administered at 3 h prior to the intraperitoneal injection of LPS (4 mg/kg) in PBS or PBS alone. |
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Dosage form |
1 mg/kg; i.p.; 3 hours before injection of LPS |
|
Applications |
BAM15 attenuated serum cytokines, organ damage (liver enzymes and serum creatinine) and tissue cytokines (liver and kidney), and reduced inflammatory mononuclear/macrophages in the liver, in part by enhancing phosphorylated αAMPK. |
|
References: [1]. Alexopoulos SJ, Chen SY, et,al. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice. Nat Commun. 2020 May 14;11(1):2397. doi: 10.1038/s41467-020-16298-2. PMID: 32409697; PMCID: PMC7224297. |
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| Cas No. | 210302-17-3 | SDF | |
| Canonical SMILES | FC(C=CC=C1)=C1NC2=NC3=NON=C3N=C2NC4=C(C=CC=C4)F | ||
| 分子式 | C16H10F2N6O | 分子量 | 340.29 |
| 溶解度 | DMSO : 75 mg/mL (220.40 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| 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 | 2.9387 mL | 14.6933 mL | 29.3867 mL |
| 5 mM | 0.5877 mL | 2.9387 mL | 5.8773 mL |
| 10 mM | 0.2939 mL | 1.4693 mL | 2.9387 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet