MK-0812
(Synonyms: 1,5-酐-2,3-双脱氧-3-[[(1R,3S)-3-[[7,8-二氢-3-(三氟甲基)-1,6-萘啶-6(5H)-基]羰基]-3-(1-甲基乙基)环己基]氨基]-4-O-甲基-D-赤式-戊糖醇,MK 0812; MK0812) 目录号 : GC11636
A CCR2 antagonist
Cas No.:624733-88-6
Sample solution is provided at 25 µL, 10mM.
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MK-0812 is an antagonist of chemokine receptor CCR-2 [1].
C-C chemokine receptor type 2 (CCR-2) is a chemokine receptor expressing on monocytes and macrophages and plays a critical and apparently non-redundant role in orchestrating the trafficking of monocytes to tissues [1].
In human whole blood, MK-0812 completely blocked all MCP-1 mediated response with IC50 value of 3.2 nM in a concentration dependent way, which is similar to the inhibition of 125I-MCP-1 binding by MK-0812 on isolated monocytes (IC50 4.5 nM). Also, MK-0812 resulted in a monocyte forward scatter measurement below unstimulated or basal levels. In rhesus whole blood, MK-0812 inhibited monocyte shape change with IC50 value of 8 nM. MK-0812 inhibited monocyte recruitment in a dose-dependent way which related with the inhibition of MCP-1 induced monocyte shape change [1].
In naive BALB/c mice, MK-0812 (30 mg/kg) reduced the frequency of Ly6G-Ly6Chi monocytes in the peripheral blood. In addition, MK-0812 reduced circulating Ly6Chi monocytes and increased the CCR2 ligand CCL2 in a dose-dependent way [2].
References:
[1]. Wisniewski T, Bayne E, Flanagan J, et al. Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist. J Immunol Methods, 2010, 352(1-2): 101-110.
[2]. Min SH, Wang Y, Gonsiorek W, et al. Pharmacological targeting reveals distinct roles for CXCR2/CXCR1 and CCR2 in a mouse model of arthritis. Biochem Biophys Res Commun, 2010, 391(1): 1080-1086.
Kinase experiment: | Human whole blood is collected in EDTA tubes and used within 1 h of blood collection. For antagonist treated samples, blood (200 ?L) is pre-incubated with MK-0812 (0.1% final DMSO concentration) for 30 min at room temperature. After which, 20 ?L of FITC conjugated anti-CD14 antibody and 4 ?L of chemokine or buffer is added to each sample and mixed lightly. An aliquot (100 ?L) of the blood mixture is incubated for 10 min at 37°C, immediately placed on ice and lightly fixed with 250 ?L of ice cold fixative (49 mL PBS, 1.0 mL 4% para-formaldehyde) for 1 min. Red blood cells are lysed by adding 1.0 mL of ice cold lysis solution (0.15 M NH4Cl2, 10 mM sodium bicarbonate, and 1 mM EDTA), and incubated for 20 min on ice. After complete lysis of red blood cells, 100 ?L of 4% para-formaldehyde is added and the samples are analyzed by flow cytometry for forward scatter measurements[1]. |
Animal experiment: | Mice[2] Female BALB/c mice are used between 8 and 10 weeks of age. SCH563705 or MK0812 are administered in a 0.4% MC solution by 30 mg/kg oral gavage (p.o.). Two hours later, the frequency of CD11b+Ly6G-Ly6Chi monocytes and CD11b+Ly6G+Ly6C+ neutrophils is determined by flow cytometry. |
References: [1]. Wisniewski T, et al. Assessment of chemokine receptor function on monocytes in whole blood: In vitro and ex vivo evaluations of a CCR2 antagonist.J Immunol Methods. 2010 Jan 31;352(1-2):101-10. | |
| Cas No. | 624733-88-6 | SDF | |
| 别名 | 1,5-酐-2,3-双脱氧-3-[[(1R,3S)-3-[[7,8-二氢-3-(三氟甲基)-1,6-萘啶-6(5H)-基]羰基]-3-(1-甲基乙基)环己基]氨基]-4-O-甲基-D-赤式-戊糖醇,MK 0812; MK0812 | ||
| 化学名 | (1-isopropyl-3-((3-methoxytetrahydro-2H-pyran-4-yl)amino)cyclopentyl)(3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)methanone | ||
| Canonical SMILES | CC(C1(C(N2CCC3=NC=C(C(F)(F)F)C=C3C2)=O)CCC(NC4CCOCC4OC)C1)C | ||
| 分子式 | C24H34F3N3O3 | 分子量 | 469.54 |
| 溶解度 | DMF: 15 mg/ml,DMF:PBS (pH 7.2) (1:20): 0.04 mg/ml,DMSO: 1 mg/ml,Ethanol: 10 mg/ml | 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 | 2.1297 mL | 10.6487 mL | 21.2974 mL |
| 5 mM | 0.4259 mL | 2.1297 mL | 4.2595 mL |
| 10 mM | 0.213 mL | 1.0649 mL | 2.1297 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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