RP101988
目录号 : GC65324
RP101988是Ozanimod的主要活性代谢产物，是一种高选择性、强效的 S1PR1（1-磷酸鞘氨醇受体1）激动剂，其对 S1PR1 和 S1PR5 的EC50分别为 0.19nM和 32.8nM。
Cas No.:2990018-57-8
Sample solution is provided at 25 µL, 10mM.
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RP101988 is the major active metabolite of Ozanimod and is a highly selective, potent agonist of the S1PR1 (sphingosine-1-phosphate receptor 1), with EC50s of 0.19nM and 32.8nM for S1PR1 and S1PR5, respectivlely[1]. Its selectivity for S1PR1 is significantly higher than that for other S1P receptor subtypes. S1PR1 plays a key regulatory role in the immune system, vascular endothelium, and nervous system. RP101988 can activate S1PR1, causing lymphocytes (T/B cells) to remain in lymphoid organs (such as lymph nodes and thymus), reducing their entry into the bloodstream and inflammatory sites[2].
In vitro, RP101988 (1μM) and other active metabolites of Ozanimod treated S1PR1-GFP overexpressing HEK-293 cells for 24 hours, showing similar pharmacological characteristics to their parent compounds[3]. Ozanimod is a weak substrate of P-glycoprotein (P-gp), while RP101988 is a substrate of P-gp and breast cancer resistance protein (BCRP) drug transporters[4].
References:
[1] Tran JQ, et al. Cardiac Safety of Ozanimod, a Novel Sphingosine-1-Phosphate Receptor Modulator: Results of a Thorough QT/QTc Study. Clin Pharmacol Drug Dev. 2018;7(3):263-276.
[2] Pérez-Jeldres T, Alvarez-Lobos M, Rivera-Nieves J. Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis. Drugs. 2021 Jun;81(9):985-1002.
[3] Selkirk JV, Yan YG, Ching N, Paget K, Hargreaves R. In vitro assessment of the binding and functional responses of ozanimod and its plasma metabolites across human sphingosine 1-phosphate receptors. Eur J Pharmacol. 2023;941:175442.
[4] Bencardino S, D'Amico F, Faggiani I, Bernardi F, Allocca M, Furfaro F, Parigi TL, Zilli A, Fiorino G, Peyrin-Biroulet L, Danese S. Efficacy and Safety of S1P1 Receptor Modulator Drugs for Patients with Moderate-to-Severe Ulcerative Colitis. J Clin Med. 2023 Jul 30;12(15):5014.
RP101988是Ozanimod的主要活性代谢产物，是一种高选择性、强效的 S1PR1（1-磷酸鞘氨醇受体1）激动剂，其对 S1PR1 和 S1PR5的EC50分别为0.19nM和 32.8nM[1]。它对 S1PR1 的选择性明显高于其他 S1P 受体亚型。S1PR1主要在免疫系统、血管内皮、神经系统中发挥关键调控作用。RP101988可以通过激活 S1PR1 ，促使淋巴细胞（T/B 细胞）滞留于淋巴器官（如淋巴结、胸腺），减少其进入血液循环和炎症部位[2]。
在体外，RP101988（1μM）以及其他Ozanimod的活性代谢物处理S1PR1-GFP过表达的HEK-293细胞24h，显示出与其母体化合物相似的药理学特征[3]。Ozanimod是P-糖蛋白（P-gp）的弱底物，而 RP101988 是P-gp和乳腺癌耐药蛋白（BCRP）药物转运蛋白的底物[4]。
| Cell experiment [1]: | |
Cell lines | HEK-293 cells |
Preparation Method | Agonist-mediated sphingosine 1-phosphate receptor 1 internalization was assessed using HEK-293 cells overexpressing sphingosine 1-phosphate receptor 1-green fluorescent protein. 3.The cells were separated using TrypLE and subjected to FACS reaction, which was then analyzed on a flow cytometer. |
Reaction Conditions | 1μM; 1、3、6 or 24 hours |
Applications | Ozanimod and its active plasma metabolites cause strong and effective internalization of sphingosine 1-phosphate receptor 1, with potency slightly increasing with prolonged exposure time. The response magnitude of each active metabolite is usually similar, and RP101988 is the most effective in inducing internalization of sphingosine 1-phosphate receptor 1 at each evaluated time point (up to 24 hours). |
References: | |
| Cas No. | 2990018-57-8 | SDF | Download SDF |
| 分子式 | C23H22N4O4 | 分子量 | 418.45 |
| 溶解度 | DMSO : 125 mg/mL (298.72 mM; Need ultrasonic) | 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 | 2.3898 mL | 11.9489 mL | 23.8977 mL |
| 5 mM | 0.478 mL | 2.3898 mL | 4.7795 mL |
| 10 mM | 0.239 mL | 1.1949 mL | 2.3898 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet