MK 0893
(Synonyms: N-[4-[(1S)-1-[3-(3,5-二氯苯基)-5-(6-甲氧基-2-萘基)-1H-吡唑-1-基]乙基]苯甲酰]-BETA-丙氨酸,MK0893; MK-0893) 目录号 : GC14793
MK 0893 是一种有效的选择性胰高血糖素受体拮抗剂，IC50 为 6.6 nM，对 GIPR、PAC1、GLP-1R、VPAC1 和 VPAC2 的选择性 > 200 倍。
Cas No.:870823-12-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Kinase experiment [1]: | |
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Binding assays |
A CHO cell line expressing the human glucagon receptor (CHO hGCGR) was maintained and membranesprepared as described in Chicchi et al. Membranes (2-5 μg) were incubated in buffer containing 50 mM Tris, pH 7.5, 5 mM MgCl2, 2 mM EDTA, 1% bovine serum albumin, 12% glycerol, 0.2 mg of wheat germ agglutinin-coated polyvinyltoluene scintillation proximity assay beads, increasing concentration of MK 0893 (diluted in 100% DMSO and added to the assay at a final concentration of 2.5%), and 50 pM 125I-glucagon. The assay was incubated for 3 h at room temperature, and the total bound radioactivity was measured with a Wallac-Microbeta counter. Nonspecific counts were determined using 1 μM unlabeled glucagon. Data were analyzed using the nonlinear regression analysis software GraphPad Prism, v4. |
| Cell experiment [1]: | |
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Cell lines |
CHO cells expressing the hGCGR. |
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Preparation method |
Dissolved in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
56-1000 nM; 30 min. |
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Applications |
In CHO cells expressing the hGCGR, MK 0893 dose dependently rightshifts the EC50 of glucagon without changing the maximum effect of glucagon. MK 0893 inhibits cAMP production. |
| Animal experiment [1]: | |
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Animal models |
hGCGR ob/ob mice. |
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Dosage form |
3, 10, and 30 mpk;1 h; administrated orally. |
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Applications |
MK 0893 reduces glucose elevation stimulated by glucagon (15 μg/kg) by 30%, 56%, and 81% at 3, 10, and 30 mpk, respectively. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Xiong Y, Guo J, Candelore MR, et al. Discovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes. J Med Chem, 2012, 55(13): 6137-6148. |
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MK 0893 is an inhibitor of both glucagon receptor and IGF-1R with IC50 values of 6.6nM and 6nM, respectively [1, 2].
In a receptor binding assay using a membrane preparation from a CHO cell line expressing the human GCGR, MK 0893 is shown to inhibit the bing between glucagon and the GCGR(IC50 value of 6.6 ± 3.5nM) and subsequently induce cAMP production(IC50 value of 15.7 ± 5.4nM). MK 0893 is proved to be a competitive, reversible GCGR antagonist, as evidenced by Schild Analysis in this cell line. And in an acute glucagon challenge model in hGCGR mice, MK 0893 is found to be active in blunting glucagon-induced glucose excursion. All these effects make MK 0893 be a potential oral treatment for type 2 diabetes. Additionally, MK 0893 is also reported as a potent, selective, and orally bioavailable IGF-1R inhibitor with robust in vivo efficacy in an IGF-driven mouse xenograft model. [1, 2].
References:
[1] Yusheng Xiong, Jian Guo, Mari R. Candelore, Rui Liang, Corey Miller, Qing Dallas-Yang, Guoqiang Jiang, Peggy E. McCann, Sajjad A. Qureshi, Xinchun Tong, Shiyao Sherrie Xu, Jackie Shang, Stella H. Vincent, Laurie M. Tota, Michael J. Wright, Xiaodong Yang, Bei B. Zhang, James R. Tata, and Emma R. Parmee. Discovery of a Novel Glucagon Receptor Antagonist N-[(4-{(1S)-1-[3-(3,5-Dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the Treatment of Type II Diabetes. Journal of Medicinal Chemistry. 2012, 55: 6137-6148.
[2] Meizhong Jin, Andrew Kleinberg, Andy Cooke, Prafulla C. Gokhale, Kenneth Foreman, Hanqing Dong, Kam W. Siu, Mark A. Bittner, Kristen M. Mulvihill, Yan Yao, Darla Landfair, Matthew O’Connor, Gilda Mak, Jonathan A. Pachter, Robert Wild, Maryland Rosenfeld-Franklin, Qunsheng Ji, Mark J. Mulvihill. Potent and selective cyclohexyl-derived imidazopyrazine insulin-like growth factor 1 receptor inhibitors with in vivo efficacy. Bioorganic & Medicinal Chemistry Letters. 2011, 21: 1176–1180.
| Cas No. | 870823-12-4 | SDF | |
| 别名 | N-[4-[(1S)-1-[3-(3,5-二氯苯基)-5-(6-甲氧基-2-萘基)-1H-吡唑-1-基]乙基]苯甲酰]-BETA-丙氨酸,MK0893; MK-0893 | ||
| 化学名 | 3-[[4-[(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)pyrazol-1-yl]ethyl]benzoyl]amino]propanoic acid | ||
| Canonical SMILES | CC(C1=CC=C(C=C1)C(=O)NCCC(=O)O)N2C(=CC(=N2)C3=CC(=CC(=C3)Cl)Cl)C4=CC5=C(C=C4)C=C(C=C5)OC | ||
| 分子式 | C32H27Cl2N3O4 | 分子量 | 588.48 |
| 溶解度 | ≥ 24.05 mg/mL in DMSO, ≥ 4.8 mg/mL in EtOH with ultrasonic and warming | 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 | 1.6993 mL | 8.4965 mL | 16.9929 mL |
| 5 mM | 0.3399 mL | 1.6993 mL | 3.3986 mL |
| 10 mM | 0.1699 mL | 0.8496 mL | 1.6993 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。