CXCR7 modulator 2
目录号 : GC34339
CXCR7modulator2是CXCR7的调节剂，其Ki值为13nM。
Cas No.:2227426-37-9
Sample solution is provided at 25 µL, 10mM.
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CXCR7 modulator 2 is a modulator of C-X-C Chemokine Receptor Type 7 (CXCR7), with a Ki of 13 nM.
CXCR7 modulator 2 (compound 18) demonstrates potent CXCR7-binding affinity (Ki=13 nM) and β-arrestin activity (EC50=11 nM). CXCR7 modulator 2 also exhibits improved selectivity in the GPCR panel and an improved therapeutic index in the hERG patch-clamp assay in comparison with 11c. CXCR7 modulator 2 exhibits moderate to high in vitro turn over in both NADPH-supplemented mouse-liver microsomes (MLM, 93 μL/min/mg) and hepatocytes (28 μL/min per million cells), shows poor passive absorptive permeability in the MDCK II-permeability assay, and has good aqueous solubility. CXCR7 modulator 2 is rapidly absorbed with a mean maximal plasma concentration (Cmax) of 682 ng/mL, which occurrs at 0.25 h (Tmax). The corresponding mean area under the plasma-concentration-versus-time profile (AUC) is 740 ng/mL/h[1].
The administration of isoproterenol for 9 days leads to the development of cardiac fibrosis, as attested by the approximately 4-fold increase in collagen deposition relative to that in the control, which is detected by picrosirius-red staining. Treatment with CXCR7 modulator 2 results in a statistically significant reduction in cardiac fibrosis, thereby demonstrating the protective role of CXCR7 modulation with CXCR7 modulator 2 in an isoproterenol-induced cardiac injury[1].
[1]. Menhaji-Klotz E, et al. Discovery of a Novel Small-Molecule Modulator of C-X-C Chemokine Receptor Type 7 as a Treatment for Cardiac Fibrosis. J Med Chem. 2018 Apr 26;61(8):3685-3696.
Cell experiment: | Measurements of potassium currents in HEK293 cells are stably transfected with the hERG channel[1]. |
Animal experiment: | Mice[1]A total of 60 male BALB/c mice (8 weeks of age) are randomized into four study groups. In two groups, isoproterenol (5 mg/kg) is administered subcutaneously once daily for 9 days to induce cardiac fibrosis. In addition, the mice in these two groups are further treated twice daily throughout the 9 day study duration with either CXCR7 modulator 2 at 30 mg/kg (n=20) or the vehicle (n=20). The mice in the third group receives PBS and the vehicle and thus serves as controls (n=15). The fourth group (n=5), which receives both isoproterenol and CXCR7 modulator 2, are used for blood sampling at 1 and 9 h postdose on days 1, 3, 6, and 9 (1 h only) to provide an overall estimate of CXCR7 coverage relative to mouse Ki. The exposures to CXCR7 modulator 2 achieved in the BALB/c mice at the 30 mg/kg dose are approximately as expected, with the unbound Cave>95% target coverage[1]. |
References: [1]. Menhaji-Klotz E, et al. Discovery of a Novel Small-Molecule Modulator of C-X-C Chemokine Receptor Type 7 as a Treatment for Cardiac Fibrosis. J Med Chem. 2018 Apr 26;61(8):3685-3696. | |
| Cas No. | 2227426-37-9 | SDF | |
| Canonical SMILES | O=C([C@@H]1[C@H](O2)CC[C@H]2C1)N3CCC([C@H](CC(N)=O)N4CCCN(C5=C(CC)C=CN6C5=NC=C6)CC4)CC3 | ||
| 分子式 | C29H42N6O3 | 分子量 | 522.68 |
| 溶解度 | DMSO: 250 mg/mL (478.30 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 | 1.9132 mL | 9.5661 mL | 19.1322 mL |
| 5 mM | 0.3826 mL | 1.9132 mL | 3.8264 mL |
| 10 mM | 0.1913 mL | 0.9566 mL | 1.9132 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