MK8722
(Synonyms: (3S,3AS,6S,6AS)-6-((5-([1,1'-联苯]-4-基)-6-氯-1H-咪唑并[4,5-B]吡啶-2-基)氧基)六氢呋喃[3,2-B]呋喃-3-醇) 目录号 : GC31470
MK8722是一种口服变构泛AMPK激活剂，能够调节葡萄糖稳态，EC50值在1-60nM范围内。
Cas No.:1394371-71-1
Sample solution is provided at 25 µL, 10mM.
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MK8722 is an orally allosteric pan-AMPK activator that supports glucose homeostasis, with EC50 values of 1-60nM[1]. MK8722 binds to the allosteric drug and metabolite (ADaM) site between the α-kinase domain and the β-glycogen-binding domain, stabilizes the enzyme’s activation loop in an active conformation, and allows bypassing the need for AMPKα T172 phosphorylation for full enzyme activation [2]. MK8722 has been widely used in animal models to regulate blood glucose levels and glucose uptake[3].
In vitro, MK8722 treatment for 48h significantly inhibited the proliferation of A2780, OV90, and SKOV3 cells with IC50 values of 35.47, 36.44 and 47.89μg/ml, respectively[4]. Treatment of PANC-1 cells with 50μM MK8722 for 24h significantly reduced colony formation and inhibited cell invasion and migration[5]. Pretreatment with 10μM MK8722 for 30min reduced the abundance of Bax, Caspase-3, and the Bax/Bcl-2 ratio and increased the abundance of SIRT3 and MnSOD activity in H2O2-induced bovine mammary alveolar cells (MAC-T)[6].
In vivo, MK8722 treatment via daily subcutaneous injection at a dose of 30mg/kg for 4 weeks in 4-month-old male HSALR mice improved the alternative splicing of Atp2a1 in the tibialis anterior muscle and resulted in the activation of AMPK and a switch of oxidative metabolism[7]. Daily oral administration of MK8722 at a dose of 30mg/kg for 30 days attenuated paclitaxel-induced hyperalgesia in male and female mice[8].
References:
[1] Myers R W, Guan H P, Ehrhart J, et al. Systemic pan-AMPK activator MK-8722 improves glucose homeostasis but induces cardiac hypertrophy[J]. Science, 2017, 357(6350): 507-511.
[2] Doshi H, Spengler K, Godbole A, et al. AMPK protects endothelial cells against HSV-1 replication via inhibition of mTORC1 and ACC1[J]. Microbiology Spectrum, 2023, 11(5): e00417-23.
[3] Feng D, Biftu T, Romero F A, et al. Discovery of MK-8722: a systemic, direct pan-activator of AMP-activated protein kinase[J]. ACS medicinal chemistry letters, 2018, 9(1): 39-44.
[4] Wang L, Zhu H, Shi Z, et al. MK8722 initiates early-stage autophagy while inhibiting late-stage autophagy via FASN-dependent reprogramming of lipid metabolism[J]. Theranostics, 2024, 14(1): 75.
[5] Wang C, Huang B, Sun L, et al. MK8722, an AMPK activator, inhibiting carcinoma proliferation, invasion and migration in human pancreatic cancer cells[J]. Biomedicine & Pharmacotherapy, 2021, 144: 112325.
[6] Liu L, Lu O, Li D, et al. Sirtuin 3 mitigates oxidative-stress-induced apoptosis in bovine mammary epithelial cells[J]. Journal of Dairy Science, 2023, 106(10): 7266-7280.
[7] Ravel‐Chapuis A, Fahmi C, Gobin J, et al. The AMPK allosteric activator MK‐8722 improves the histology and spliceopathy in myotonic dystrophy type 1 (DM1) skeletal muscle[J]. The FASEB Journal, 2024, 38(23): e70199.
[8] Inyang K E, McDougal T A, Ramirez E D, et al. Alleviation of paclitaxel-induced mechanical hypersensitivity and hyperalgesic priming with AMPK activators in male and female mice[J]. Neurobiology of Pain, 2019, 6: 100037.
MK8722是一种口服变构泛AMPK激活剂，能够调节葡萄糖稳态，EC50值在1-60nM范围内[1]。MK8722通过结合于AMPK的变构药物和代谢物位点（位于α激酶结构域和β糖原结合结构域之间），稳定酶激活环的活性构象，从而绕过AMPKα T172磷酸化以实现酶完全激活[2]。MK8722已广泛应用于动物模型中，用于调节血糖水平和葡萄糖摄取[3]。
在体外，MK8722处理48小时能显著抑制A2780、OV90和SKOV3细胞的增殖，IC50值分别为35.47、36.44和47.89μg/ml[4]。用50μM的MK8722处理PANC-1细胞24小时，可显著减少细胞克隆形成，并抑制细胞侵袭和迁移能力[5]。在过氧化氢诱导的牛乳腺肺泡细胞中，用10μM的MK8722预处理30分钟，能够降低Bax、Caspase-3的丰度及Bax/Bcl-2比值，同时提高SIRT3的丰度和MnSOD活性[6]。
在体内，对4月龄雄性HSALR小鼠每日皮下注射30mg/kg剂量的MK8722，连续4周，可改善胫骨前肌中Atp2a1基因的可变剪接，并导致AMPK 的激活和氧化代谢的转变[7]。每日以30mg/kg剂量口服MK8722，连续30天，能够减轻紫杉醇诱导的雄性和雌性小鼠痛觉过敏[8]。
| Cell experiment [1]: | |
Cell lines | A2780 cells |
Preparation Method | A2780 cells were cultured in complete Dulbecco's modified Eagle's medium (DMEM) supplemented with 100µg/ml streptomycin, 100U/ml penicillin, and 10% fetal bovine serum (FBS) at 37°C in 5% CO2. Cells were seeded in 96-well plates at a density of approximately 3×103 cells/well and incubated for 24 hours. Subsequently, cells were treated with MK8722 (5, 10, 20, 40, 60, 80, and 100μM) for 48 hours. The CCK-8 solution was diluted in the medium at a ratio of 1:10 and added to a 96-well plate. After 2h of incubation, cell viability was determined. |
Reaction Conditions | 5, 10, 20, 40, 60, 80, and 100μM; 48h |
Applications | MK8722 treatment inhibited the cell viability of A2780 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male BALB/c nude mice |
Preparation Method | Male nude mice (BALB/c), weighing 18-22g, aged 6-8 weeks, were housed in a temperature, humidity, and light-controlled environment and fed a standard mouse diet and water. Experimental mice (n=3) were subcutaneously injected with 5×106 PANC-1 cells dissolved in 100μl PBS into the root of the right lower limb, followed by daily gavage of MK8722 (25mg/kg/day) for 30 days. Control mice (n=3) were injected with 5×106 PANC-1 cells and gavaged with control vehicle (DMSO) daily. Tumor length and width were measured every other day, and tumor volume was calculated using the formula V=(length×width2)/2, where length was always the longest dimension of the tumor. |
Dosage form | 25mg/kg/day for 30 days; p.o. |
Applications | MK8722 treatment significantly inhibited tumor volume and weight in mice. |
References: | |
| Cas No. | 1394371-71-1 | SDF | |
| 别名 | (3S,3AS,6S,6AS)-6-((5-([1,1'-联苯]-4-基)-6-氯-1H-咪唑并[4,5-B]吡啶-2-基)氧基)六氢呋喃[3,2-B]呋喃-3-醇 | ||
| Canonical SMILES | O[C@H]1[C@@]([C@]2([H])OC1)([H])OC[C@H]2OC3=NC4=NC(C(C=C5)=CC=C5C6=CC=CC=C6)=C(Cl)C=C4N3 | ||
| 分子式 | C24H20ClN3O4 | 分子量 | 449.89 |
| 溶解度 | DMSO : ≥ 62.5 mg/mL (138.92 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 | 2.2228 mL | 11.1138 mL | 22.2277 mL |
| 5 mM | 444.6 μL | 2.2228 mL | 4.4455 mL |
| 10 mM | 222.3 μL | 1.1114 mL | 2.2228 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
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- Purity: >98.00%
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