MLi-2
(Synonyms: REL-3-[6-[(2R,6S)-2,6-二甲基-4-吗啉基]-4-嘧啶基]-5-[(1-甲基环丙基)氧基]-1H-吲唑) 目录号 : GC30769
An LRRK2 inhibitor
Cas No.:1627091-47-7
Sample solution is provided at 25 µL, 10mM.
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MLi-2 is an inhibitor of leucine-rich repeat kinase 2 (LRRK2; IC50 = 0.76 nM).1 It is greater than 100-fold selective for LRRK2 over a panel of 308 protein kinases, as well as a panel of receptors and ion channels, at 10 ?M. It increases glucocerebrosidase (GCase) activity in dopaminergic neurons differentiated from induced pluripotent stem cells generated from skin fibroblasts isolated from patients with Parkinson's disease expressing LRRK2 mutations when used at a concentration of 600 nM.2 Dietary administration of MLi-2 (30 mg/kg per day) inhibits cortical LRRK2 phosphorylation in the MitoPark mouse model of Parkinson's disease.1
1.Fell, M.J., Mirescu, C., Basu, K., et al.MLi-2, a potent, selective, and centrally active compound for exploring the therapeutic potential and safety of LRRK2 kinase inhibitionJ. Pharmacol. Exp. Ther.355(3)397-409(2015) 2.Ysselstein, D., Nguyen, M., Young, T.J., et al.LRRK2 kinase activity regulates lysosomal glucocerebrosidase in neurons derived from Parkinson's disease patientsNat. Commun.10(1)5570(2019)
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Animal experiment: |
Mice: MLi-2 is suspended in 30% Captisol and administered in a volume of 10 mL/kg. Dose calculations are on the basis of active moiety. Mice receive MLi-2 [1-100 mg/kg; by mouth (PO)], or vehicle 1 hour prior to euthanasia by excess CO2. Immediately following euthanasia, mouse brain cortex is dissected and frozen on a steel plate over dry ice for analysis of pSer935 LRRK2 via Western Blot. Plasma and brain samples are collected and frozen for determination of MLi-2 levels by LC-MS/MS[1]. |
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References: [1]. Fell MJ, et al. MLi-2, a Potent, Selective, and Centrally Active Compound for Exploring the Therapeutic Potential and Safety of LRRK2 Kinase Inhibition. J Pharmacol Exp Ther. 2015 Dec;355(3):397-409. |
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| Cas No. | 1627091-47-7 | SDF | |
| 别名 | REL-3-[6-[(2R,6S)-2,6-二甲基-4-吗啉基]-4-嘧啶基]-5-[(1-甲基环丙基)氧基]-1H-吲唑 | ||
| Canonical SMILES | C[C@@](C1)([H])O[C@](C)([H])CN1C2=CC(C3=NNC4=CC=C(OC5(C)CC5)C=C43)=NC=N2 | ||
| 分子式 | C21H25N5O2 | 分子量 | 379.46 |
| 溶解度 | DMSO : ≥ 26 mg/mL (68.52 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 | 2.6353 mL | 13.1766 mL | 26.3532 mL |
| 5 mM | 0.5271 mL | 2.6353 mL | 5.2706 mL |
| 10 mM | 0.2635 mL | 1.3177 mL | 2.6353 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet