Ceralifimod
(Synonyms: ONO-4641) 目录号 : GC18348An agonist of S1P1 and S1P5 receptors
Cas No.:891859-12-4
Sample solution is provided at 25 µL, 10mM.
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Ceralifimod (ONO-4641) is selective, high potent agonist for sphingosine 1-phosphate receptors 1 and 5, with EC50s of 27.3, 334 pM for human S1P receptor 1 and 5, respectively.
Ceralifimod (ONO-4641) has an agonistic action for S1P1 and S1P5, and there is no difference between human and rat in the agonistic action of Ceralifimod (ONO-4641) for S1P1. Ceralifimod (ONO-4641) also induces S1P1 down-regulation in a concentration-dependent manner and by approximately 90% at concentration of 25 nM[1].
The clinical scores of the Ceralifimod (ONO-4641) 0.03 and 0.1 mg/kg groups remain lower than that in the control group. The maximum clinical scores decrease dose-dependently in the Ceralifimod (ONO-4641) groups and those in the Ceralifimod (ONO-4641) 0.03 and 0.1 mg/kg groups are significantly lower than that in the control group. Specifically, paralysis is inhibited completely in seven of eight animals in the Ceralifimod (ONO-4641) 0.1 mg/kg group.In normal NOD mice, the number of peripheral blood lymphocytes is decreased by approximately 20, 60 and 80% at 24 h after a single oral dose of 0.01, 0.03 and 0.1 mg/kg of Ceralifimod (ONO-4641), respectively. In the control group of the NOD mouse model of relapsing-remitting EAE, the relapse rate is 90.0%, and two of the nine animals die. The cumulative clinical score in the control group is 65.4±18.50. In contrast, none of animals in the Ceralifimod (ONO-4641) 0.1 mg/kg group have a relapse; that is, Ceralifimod completely prevents relapse at a dose of 0.1 mg/kg. In the Ceralifimod (ONO-4641) groups, two of the nine animals in the 0.01 mg/kg die[1].
References:
[1]. Komiya T, et al. Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin Exp Immunol. 2013 Jan;171(1):54-62.
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Animal experiment: |
Rats[1]Female Lewis rats are immunized by subcutaneous administration of the inducer at a volume of 0.1 mL into the footpad. Ceralifimod (ONO-4641: 0.01, 0.03 and 0.1 mg/kg), prednisolone (3 mg/kg) or 0.5% MC is administered orally once daily from immunization days 4-21. More specifically, the severity of paralysis is graded on a scoring scale to determine the clinical score. Mouse[1]NOD mice are immunized into the left footpad with the inducer at a volume of 0.05 mL. A second PTX injection is administered 48 h later. Animals that achieve remission after the initial onset are selected and grouped, and Ceralifimod (ONO-4641: 0.01, 0.03 or 0.1 mg/kg) or 0.5% MC is administered orally to each group once daily for 8 weeks. Neurological symptoms are graded according to the degree of paralysis. A clinical score of 5 is assigned to dead animals until the end of observation[1]. |
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References: [1]. Komiya T, et al. Efficacy and immunomodulatory actions of ONO-4641, a novel selective agonist for sphingosine 1-phosphate receptors 1 and 5, in preclinical models of multiple sclerosis. Clin Exp Immunol. 2013 Jan;171(1):54-62. |
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| Cas No. | 891859-12-4 | SDF | |
| 别名 | ONO-4641 | ||
| 化学名 | 1-[[3,4-dihydro-6-[(2-methoxy-4-propylphenyl)methoxy]-1-methyl-2-naphthalenyl]methyl]-3-azetidinecarboxylic acid | ||
| Canonical SMILES | CCCC1=CC=C(COC2=CC(CCC(CN3CC(C(O)=O)C3)=C4C)=C4C=C2)C(OC)=C1 | ||
| 分子式 | C27H33NO4 | 分子量 | 435.6 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 5 mg/ml,DMSO:PBS (pH 7.2)(1:9): 0.1 mg/ml,Ethanol: slightly soluble | 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 | 2.2957 mL | 11.4784 mL | 22.9568 mL |
| 5 mM | 0.4591 mL | 2.2957 mL | 4.5914 mL |
| 10 mM | 0.2296 mL | 1.1478 mL | 2.2957 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: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet