MK-28
目录号 : GC61072
MK-28是一种有效且选择性的胰腺内质网激酶（PERK）激动剂，通过调节内质网应激反应发挥作用。
Cas No.:864388-65-8
Sample solution is provided at 25 µL, 10mM.
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MK-28 is a potent and selective agonist of pancreatic endoplasmic reticulum kinase (PERK), which functions by modulating the endoplasmic reticulum stress response[1]. MK-28 exhibits favorable pharmacokinetic properties and has the ability to cross the blood-brain barrier[2]. MK-28 has been shown to improve motor and executive function, as well as effectively extend the survival period, in a Huntington's disease mouse model[3].
In vitro, pretreatment of STHdhQ111/111 striatal cells (a Huntington's disease model) with MK-28 (5-100μM) for 48 hours significantly reduced endoplasmic reticulum stress-induced apoptosis, while concurrently increasing the levels of eIF2α phosphorylation and ATF4 protein expression[2].
In vivo, administration of MK-28 (0.3-1mg/kg) via intraperitoneal injection three times per week, starting from 3 weeks of age in R6/2 Huntington's disease model mice, significantly ameliorated motor dysfunction and extended their survival[3].
References:
[1] Costa MFD, Höglinger GU, Rösler TW. Development of a cell-free screening assay for the identification of direct PERK activators. PLoS One. 2023 May 18;18(5):e0283943.
[2] Ganz J, Shacham T, Kramer M, et al. A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models. Sci Rep. 2020 Apr 23;10(1):6875.
[3] Shacham T, Offen D, Lederkremer GZ. Efficacy of therapy by MK-28 PERK activation in the Huntington's disease R6/2 mouse model. Neurotherapeutics. 2024 Mar;21(2):e00335.
MK-28是一种有效且选择性的胰腺内质网激酶（PERK）激动剂，通过调节内质网应激反应发挥作用[1]。MK-28具备良好的药代动力学特性，并能透过血脑屏障[2]。MK-28能够改善亨廷顿病模型小鼠的运动与执行功能，并有效延长其生存期[3]。
在体外，MK-28（5-100μM）预处理STHdhQ111/111亨廷顿病模型纹状体细胞48小时，显著降低内质网应激诱导的细胞凋亡，同时增加eIF2α磷酸化水平和ATF4蛋白表达[2]。
在体内，MK-28（0.3-1mg/kg）通过每周三次腹腔注射处理3周龄开始的R6/2亨廷顿病模型小鼠，显著改善运动功能障碍并延长生存期[3]。
| Cell experiment [1]: | |
Cell lines | STHdhQ111/111 cells (murine striatal cell line expressing full-length polyQ-expanded mutant huntingtin) |
Preparation Method | STHdhQ111/111 cells were incubated with the ER stress-inducer tunicamycin (Tun) and in parallel with increasing concentrations of MK-28 (5-100μM). Apoptosis was measured after 48h of Tun exposure. |
Reaction Conditions | 5-100μM; 48 hours |
Applications | MK-28 strongly protected cells from ER stress-induced apoptosis in a dose-dependent manner, reducing apoptosis by 5-fold at 100μM. |
| Animal experiment [2]: | |
Animal models | B6CBA R6/2 Huntington's disease model mice |
Preparation Method | Mice were treated from the age of 3 weeks by intraperitoneal injection 3 times a week with different doses of MK-28 (0.1, 1, and 10mg/kg). Body weight and blood glucose levels were monitored weekly. |
Dosage form | 0.1, 1, and 10mg/kg; i.p. |
Applications | MK-28 showed a positive influence on body weight, significantly slowing down weight loss at 1mg/kg at 12 weeks of age. Blood glucose levels, which were significantly increased in Huntington's disease mice, returned to regular levels or slightly below in all treated groups at 8 weeks of age. |
References: | |
| Cas No. | 864388-65-8 | SDF | |
| Canonical SMILES | OC1=CC=C(C=C1O)/C=N/N(C2=NC(C3=CC=CC=C3)=CC(C4=CC=CC=C4)=N2)C | ||
| 分子式 | C24H20N4O2 | 分子量 | 396.44 |
| 溶解度 | DMSO: 12.5 mg/mL (31.53 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 | 2.5224 mL | 12.6122 mL | 25.2245 mL |
| 5 mM | 504.5 μL | 2.5224 mL | 5.0449 mL |
| 10 mM | 252.2 μL | 1.2612 mL | 2.5224 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%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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