Ozanimod

製品コードS7952 バッチS795201

印刷

化学情報

Synonyms

RPC1063

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₃H₂₄N₄O₃

分子量

404.46

CAS No.

1306760-87-1

Solubility (25°C)*

体外

DMSO

40 mg/mL (98.89 mM)

Ethanol

10 mg/mL (24.72 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution

5%DMSO 1 Corn oil

2.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL of 40 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Ozanimod is a selective oral S1P Receptor 1 modulator. Phase 3.
in vitro	In S1P1R-HEK293T cells, Ozanimod induces sustained S1P1R internalization and degradation. ^[1]
in vivo	In vivo, Ozanimod shows high oral bioavailability and volume of distribution. In a MOG-induced EAE mouse model, Ozanimod (3 mg/kg, p.o.) suppresses clinical symptoms. In a rat TNBS model of inflammatory bowel disease, Ozanimod (1.2 mg/kg, p.o.) inhibits clinical and histological disease scores. In a Naïve CD4+CD45Rbhi T cell adoptive transfer model, Ozanimod (1.2 mg/kg, p.o.) also significantly reduced disease severity as assessed by measuring the degree of inflammation, gland loss, hyperplasia, neutrophil infiltrate and mucosal thickness. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro pharmacology assays
キナーゼアッセイ	Cell signaling assays used the LiveBLAzer-FRET B/G assay to detect cAMP (S1P1R) or β-arrestin signaling (S1P4R). Assays are performed in 384-well plates in triplicate according to manufacturer directions. Compound stocks are stored at 10 mM in 100% DMSO at -80°C, and initially diluted 1:10 with 20% (2-hydoxypropyl)-β-cyclodextrin. A 10-point dose response curve is generated at 40-times the final assay concentration in 10 mM Hepes pH 7.4, containing 0.1% Pluronic F-127. For the S1P1R assay, 80 μM forskolin is included in the diluent. Briefly, 10⁴ cells/well are incubated with a dose response of ligand at 37°C for 4 hrs. CC4-AM substrate and probenecid are added and incubated at 37°C for a further 2 hrs and analyzed with a SpectramaxM5. For S1P1R cAMP assays, data is normalized to the maximum fluorescence generated by 2 μM forskolin. For GTPγS binding assays, 1-5μg/well of membrane protein is incubated with 10 μM GDP, 100-500 μg/well Wheat Germ Agglutinin PVT SPA beads in 50 mM HEPES, 100 mM NaCl, 10 mM MgCl₂, 20 μg/ml saponin and 0.1% fatty acid free BSA for 15 minutes in 96-well plates. After the addition of compound and 200 pM GTP [35S] 1250Ci/mmol), the plates are incubated for 120 minutes and centrifuged at 300g for 5 minutes. Radioactivity is detected with a TopCount Instrument. All data is fit with a four parameter variable slope non-linear regression (GraphPad Prism) to generate half-maximal effective concentration (EC50) and maximum efficacy relative to S1P.
細胞アッセイ	細胞株	HEK293T cells
	濃度	1 μM
	反応時間	1 h
	実験の流れ	Cells expressing S1P1 receptors were incubated with vehicle control or 1 μM RPC1063 for 1 h.
動物実験	動物モデル	MOG-induced EAE model in C57Bl6 mice, TNBS model of inflammatory bowel disease in male Sprague Dawley rats, and Na飗e CD4+CD45Rbhi T cell adoptive transfer model in SCID mice
	投薬量	0.1-3 mg/kg
	投与方法	p.o.

参考

[1] Scott FL, et al. Br J Pharmacol. 2016. doi: 10.1111/bph.13476.

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Ponesimod inhibits astrocyte-mediated neuroinflammation and protects against cingulum demyelination via S1P1 -selective modulation [ FASEB J, 2022, 36(2):e22132]	PubMed: 34986275
Role and Mechanism of Ozanimod (RPC1063) in Oligodendrocyte Precursor Cell Differentiation [ China Biotechnology, 2020, (6): 10-19]	PubMed: None
Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing. [ Nucleic Acids Res, 2019, 10.1093/nar/gkz1136]	PubMed: 31799598
Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma [ Leukemia, 2019, 10.1038/s41375-019-0478-9]	PubMed: 31097785
S1PR1 drives a feedforward signalling loop to regulate BATF3 and the transcriptional programme of Hodgkin lymphoma cells [ Leukemia, 2019, 10.1038/s41375-019-0511-z]	PubMed: 28878352
The Establishment and Validation of the Human U937 Cell Line as a Cellular Model to Screen Immunomodulatory Agents Regulating Cytokine Release Induced by Influenza Virus Infection [ Virol Sin, 2019, 34(6):648-661]	PubMed: 31286365

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。