EX229
(Synonyms: AMPK Activator 991) 目录号 : GC31411
EX229是一种苯并咪唑衍生物，是一种有效的变构激动剂作用于AMP活化蛋白激酶（AMPK）。
Cas No.:1219739-36-2
Sample solution is provided at 25 µL, 10mM.
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EX229 is a benzimidazole derivative that functions as a potent allosteric agonist of AMP-activated protein kinase (AMPK)[1]. EX229 binds to AMPK with high specificity, exhibiting differential binding affinity for various isoforms: α1β1γ1 (Kd=0.06μM), α2β1γ1 (Kd=0.06μM), and α1β2γ1 (Kd=0.51μM)[2]. EX229 effectively regulates glucose transport and inhibits lipogenesis[3].
In vitro, treatment of C2C12 myotube cells with EX229 (2–25μM) for 12 hours significantly activated the AMPK signaling pathway, as indicated by a dose-dependent increase in AMPKα phosphorylation. This was accompanied by upregulation of key unfolded protein response (UPR) markers, including ATF4 and CHOP, at the protein level[4].
In vivo, daily intramuscular administration of EX229 (2.0mg/kg) for 8 weeks in a rat model of heart failure induced by coronary artery ligation significantly reversed the cardioprotective effects of Fuyu Decoction. This was demonstrated by a marked increase in left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV), along with a significant reduction in left ventricular ejection fraction (LVEF) and fractional shortening (LVFS)[5].
References:
[1] Lai YC, Kviklyte S, Vertommen D, et al. A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators. Biochem J. 2014 Jun 15;460(3):363-75.
[2] Xiao B, Sanders MJ, Carmena D, et al. Structural basis of AMPK regulation by small molecule activators. Nat Commun. 2013;4:3017.
[3] Bultot L, Jensen TE, Lai YC, et al. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle. Am J Physiol Endocrinol Metab. 2016 Oct 1;311(4):E706-E719.
[4] Gong J, Wang L, Tao W, et al. AMPK Mediates Early Activation of the Unfolded Protein Response through a Positive Feedback Loop in Palmitate-Treated Muscle Cells. Front Biosci (Landmark Ed). 2023 Aug 7;28(8):159.
[5] Ma J, Xu Z, Zhu J, et al. Fuyu Decoction improves ventricular remodeling in rats with heart failure by inhibiting AMPK/mTOR pathway-mediated autophagy. Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):466-473.
EX229是一种苯并咪唑衍生物，是一种有效的变构激动剂作用于AMP活化蛋白激酶（AMPK）[1]。EX229能够特异性地与AMPK结合，对α1β1γ1（Kd=0.06μM）、α2β1γ1（Kd=0.06μM）和α1β2γ1（Kd=0.51μM）不同亚型的亲和力存在差别[2]。EX229能有效调节葡萄糖转运和抑制脂肪生成[3]。
在体外，EX229（2-25μM）处理C2C12肌管细胞12小时，显著激活AMPK信号通路，表现为AMPKα磷酸化水平剂量依赖性升高，同时诱导未折叠蛋白反应（UPR）关键标志物ATF4和CHOP的蛋白表达上调[4]。
在体内，EX229（2.0mg/kg）每日肌肉注射处理冠状动脉结扎诱导的心力衰竭模型大鼠8周，能够显著逆转附萸汤对心力衰竭大鼠心功能指标的改善作用，表现为左心室舒张末期容积（LVEDV）和收缩末期容积（LVESV）显著增加，左心室射血分数（LVEF）和左室短轴缩短率（LVFS）显著降低[5]。
| Cell experiment [1]: | |
Cell lines | C2C12 myotubes (mouse skeletal muscle cell line) |
Preparation Method | C2C12 myoblasts were differentiated into myotubes in high-glucose DMEM supplemented with 2% horse serum for 4 days. Myotubes were treated with EX229 at concentrations ranging from 2 to 25μM for 12 hours. |
Reaction Conditions | 2-25μM; 12 hours |
Applications | EX229 dose-dependently activated AMPK signaling, as evidenced by increased phosphorylation of AMPKα (p-AMPKα). This activation subsequently induced the unfolded protein response (UPR), marked by upregulated protein expression of UPR markers ATF4 and CHOP. EX229 also enhanced the mRNA levels of UPR-related genes, including BIP, ATF4, GADD34, and XBP1s, demonstrating EX229 role in promoting ER stress adaptation. |
| Animal experiment [2]: | |
Animal models | Male Wistar rats with heart failure induced by ligation of the left anterior descending coronary artery |
Preparation Method | Rats were treated with EX229 (2.0mg/kg) via daily intramuscular injection for 8 weeks, starting 4 weeks after heart failure induction. The treatment was combined with Fuyu Decoction (5.0g/kg, oral gavage) in the Fuyu Soup+EX229 group. |
Dosage form | 2.0mg/kg; i.m. |
Applications | EX229 administration significantly reversed the cardioprotective effects of Fuyu Decoction, exacerbating heart failure progression. EX229 increased left ventricular end-diastolic volume (LVEDV) and end-systolic volume (LVESV), reduced ejection fraction (LVEF) and fractional shortening (LVFS), and worsened ventricular remodeling indicators. EX229 also amplified myocardial infarction area, promoted cardiomyocyte apoptosis, and enhanced autophagy activation via the AMPK/mTOR pathway, as evidenced by upregulated p-AMPK, LC3-II/LC3-I, and Beclin1 expressions, and suppressed p-mTOR and p62 levels. |
References: | |
| Cas No. | 1219739-36-2 | SDF | |
| 别名 | AMPK Activator 991 | ||
| Canonical SMILES | O=C(O)C1=CC(OC2=NC3=CC(Cl)=C(C4=CC5=C(N(C)C=C5)C=C4)C=C3N2)=CC=C1C | ||
| 分子式 | C24H18ClN3O3 | 分子量 | 431.87 |
| 溶解度 | DMSO : 5.4 mg/mL (12.50 mM) | 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 | 2.3155 mL | 11.5776 mL | 23.1551 mL |
| 5 mM | 463.1 μL | 2.3155 mL | 4.631 mL |
| 10 mM | 231.6 μL | 1.1578 mL | 2.3155 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。
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- Purity: >98.00%
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