Ozanimod (RPC1063)
(Synonyms: 奥扎莫德; RPC-1063) 目录号 : GC14360
An S1P1 and S1P5 agonist
Cas No.:1306760-87-1
Sample solution is provided at 25 µL, 10mM.
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Ozanimod (RPC1063) is a high orallybioavailable agonist of the sphingosine-1-phosphate receptor subtypes 1 (S1P1) and 5 (S1P5). S1P receptors belong to the family of G-protein-coupled receptor which contains five subtypes, denoting S1P1-5. S1P receptors are involved in coronary artery caliber,endothelial integrity, cardiac function, and lymphocyte recirculation [1].
In vitro: Ozanimod(RPC1063) was a specific agonist for S1P1 and S1P5 receptors. The EC50values were 160 ± 60 pM and 410 ± 160 pM for S1P1 receptors in the inhibition of cAMP generation and[35S]-GTPγS binding. The 83% Emax value of ozanimod against S1P5 receptor was 11 ± 4.3 nM. RPC1063 dose-dependently decreased S1P1 receptor re-expression on the cell surface and resulted in near complete and sustained loss of cell surface receptor expression at concentrations above 10 nM in S1P1 receptor-HEK293T cells after 1 h incubation [1].
In vivo: The t1/2 of ozanimod was 4.7 h and 5.1 h in mice and rats after p.o. administration, respectively. About 81–82% decrease in circulating T lymphocyte was observed after dosing administration for 6 h, with a maximal blood concentration of 45 nM and 159 nM in rats and mice respectively. Oral gavage of ozanimod dose-dependently reduced the disease score of mice in both doses (0.2 or 0.6 mg/kg/day) [1].
Clinical trial: In the double-blind, placebo-controlled phase 2 trial in adult patients with moderate-to-severe ulcerative colitis, when treated with 1 mg ozanimod for 8 weeks, clinical response occurred in 57% of the patients while 0.5 mg ozanimod caused a 54% response. At week 32, the rate of clinical remission was 21% and 26% at the dose of 1 mg and 0.5 mg. The side effects were mainly anemia and headache [2].
References:
[1].Scott F L, Clemons B, Brooks J, et al. Ozanimod (RPC1063) is a potent sphingosine‐1‐phosphate receptor‐1 (S1P1) and receptor‐5 (S1P5) agonist with autoimmune disease‐modifying activity[J]. British Journal of Pharmacology, 2016.
[2].Sandborn WJ, Feagan BG1, et al. Ozanimod Induction and Maintenance Treatment for Ulcerative Colitis. N Engl J Med. 2016, 374(18):1754-1762.
Cell experiment: | Representative histograms of transfected HEK293T cells expressing S1P1 receptors incubated with vehicle control or 1 μM RPC1063. HEK293T cells are incubated with increasing doses of Ozanimod (0.01 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM and 10 μM) for 1 h, or for 1 h followed by extensive washing to remove compound, then a 24 h recovery period and cell surface receptor expression is monitored[1]. |
Animal experiment: | Mice[1]Female C57BL/6 mice (60 total, 10 weeks of age) are immunized with Myelin Oligodendrocyte Glycoproteins (MOG) 35-55 peptide with complete Freund's adjuvant on day 0, and pertussis toxin is administered 2 h and 24 h later. At the first instance of clinical symptoms of EAE (limp tail), mice are randomized into treatment groups (n=10 per group) and administered the test compound, p.o., once daily for 14 days. Mice that develop disease earlier than 9 days post-immunization are not enrolled, as these often develop fulminant disease that does not respond to therapy. Test compounds are 0.2 and 0.6 mg/kg Ozanimod, 3 mg/kg FTY720 or vehicle (5% DMSO, 5% Tween-20, 90% 0.1 N HCl). Animals are monitored daily for body weight and clinical symptoms and scored. At the end of the study, mice are anaesthetized via inhalation of isoflurane bubbled with oxygen at 10-20 kPa, blood drawn via cardiac puncture to exsanguination and analysed by a veterinary haemoanalyser. |
References: [1]. Scott FL, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1 ) and receptor-5 (S1P5 ) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016 Jun;173(11):1778-92. | |
| Cas No. | 1306760-87-1 | SDF | |
| 别名 | 奥扎莫德; RPC-1063 | ||
| 化学名 | (S)-5-(3-(1-((2-hydroxyethyl)amino)-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile | ||
| Canonical SMILES | CC(OC1=C(C#N)C=C(C2=NC(C3=CC=CC4=C3CC[C@]4([H])NCCO)=NO2)C=C1)C | ||
| 分子式 | C23H24N4O3 | 分子量 | 404.46 |
| 溶解度 | ≥ 40.4mg/mL in DMSO | 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 | 2.4724 mL | 12.3622 mL | 24.7243 mL |
| 5 mM | 0.4945 mL | 2.4724 mL | 4.9449 mL |
| 10 mM | 0.2472 mL | 1.2362 mL | 2.4724 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。
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Quality Control & SDS
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- Purity: >99.50%
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