ML604086
目录号 : GC39649
ML604086 是一种选择性的 CCR8 抑制剂，抑制循环T细胞上 CCL1 与 CCR8 结合。ML604086 抑制 CCL1 介导的趋化作用，增加细胞内 Ca2+浓度。
Cas No.:850330-18-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ML604086 is a selective CCR8 inhibitor, inhibiting CCL1 binding to CCR8 on circulating T-cells. ML604086 inhibits CCL1 mediated chemotaxis and increases in intracellular Ca2+ concentrations[1][2].
[1]. James E. Pease, et al. Chemokine Receptors in Allergy, Inflammation, and Infectious Disease. Top Med Chem (2015) 14: 1-40. [2]. Lin Wang, et al. Antagonism of chemokine receptor CCR8 is ineffective in a primate model of asthma. Thorax 2013;68:506-512.
| Cas No. | 850330-18-6 | SDF | |
| Canonical SMILES | O=C(NC1=C2C=CC=CC2=C(S(=O)(N[C@H]3[C@H](C)CN(C([C@@H](N)C)=O)CC3)=O)C=C1)C4=CC=CC=C4C | ||
| 分子式 | C27H32N4O4S | 分子量 | 508.63 |
| 溶解度 | Methanol: 125 mg/mL (245.76 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 | 1.9661 mL | 9.8303 mL | 19.6607 mL |
| 5 mM | 0.3932 mL | 1.9661 mL | 3.9321 mL |
| 10 mM | 0.1966 mL | 0.983 mL | 1.9661 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。
Antagonism of chemokine receptor CCR8 is ineffective in a primate model of asthma
Thorax 2013 Jun;68(6):506-12.PMID:23457038DOI:10.1136/thoraxjnl-2012-203012
Background: Expression of the T-cell-associated chemokine receptor CCR8 and its ligand CCL1 have been demonstrated to be elevated in patients with asthma. CCR8 deficiency or inhibition in models of allergic airway disease in mice resulted in conflicting data. Objective: To investigate the effects of a selective small molecule CCR8 inhibitor (ML604086) in a primate model of asthma. Methods: ML604086 and vehicle were administered by intravenous infusion to 12 cynomolgus monkeys during airway challenge with Ascaris suum. Samples were collected throughout the study to measure pharmacokinetics (PK) and systemic CCR8 inhibition, as well as inflammation, T helper 2 (Th2) cytokines and mucus in bronchoalveolar lavage (BAL). Airway resistance and compliance were measured before and after allergen challenge, and in response to increasing concentrations of methacholine. Results: ML604086 inhibited CCL1 binding to CCR8 on circulating T-cells>98% throughout the duration of the study. However, CCR8 inhibition had no significant effect on allergen-induced BAL eosinophilia and the induction of the Th2 cytokines IL-4, IL-5, IL-13 and mucus levels in BAL. Changes in airway resistance and compliance induced by allergen provocation and increasing concentrations of methacholine were also not affected by ML604086. Conclusions: These results clearly demonstrate a dispensable role for CCR8 in ameliorating allergic airway disease in atopic primates, and suggest that strategies other than CCR8 antagonism should be considered for the treatment of asthma.