RO9021
目录号 : GC15466
RO9021 是一种具有口服生物利用度的新型 ATP 竞争性 SYK 抑制剂，平均 IC50 为 5.6 nM。
Cas No.:1446790-62-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Kinase experiment: | The inhibitory potency to SYK is determined in a radiometric assay using inactive SYK kinase. Briefly, SYK protein is dephosphorylated by PTP1B phosphatase and then the reaction is initiated by the addition of substrate cocktail that contained 20 μM ATP, 0.025 μCi ATP-γ-33P and 10 μM biotinylated synthetic peptide. The reaction is carried out for 30 minutes and resulting 33P incorporation is determined by top counter. |
Animal experiment: | Briefly, DBA1/J male mice are injected intradermally with 0.1 mL bovine type II collagen (100 μg) and complete Freund’s adjuvant followed by second immunization on day 21 with bovine type II collagen and incomplete Freund adjuvant. RO9021 is administered orally, randomized into different groups (14 mice/groups), every day for 14 days starting on the day after second immunization. Clinical arthritis scores (1 to 4) of individual paws are assessed and the arthritic index for each mouse is determined by adding the individual scores of all four paws. The level of cytokines in serum is determined by Luminex analysis. |
References: [1]. Liao C, et al. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. | |
IC50: 5.6 nM
RO9021 is a Syk inhibitor.
Spleen tyrosine kinase (SYK) is identified as a critical integrator of intracellular signals regulated by activated immunoreceptors, such as Fc receptors and Bcell receptors (BCR), which are of great importantance for the function and development of lymphoid cells.
In vitro: Previous study found that in addition to the suppression of Bcell receptor signaling in human peripheral blood mononuclear cells and whole blood, FcγR signaling in human monocytes, and Fc R signaling in human mast cells, RO9021 could also block the in vitro osteoclastogenesis from mouse bone marrow macrophages. Moreover, the Toll-like Receptor 9 signaling in human Bcells could be blocked by RO9021, leading to the decreased levels of plasmablasts, immunoglobulin (Ig) G and IgM upon B-cell differentiation. In addition, RO9021 could also potently inhibit type I interferon production by human plasmacytoid dendritic cells (pDC) via TLR9 activation, and such effect was found to be specific to TLR9 since RO9021 did not show inhibitary effect on TLR4- or JAK-STAT-mediated signaling [1].
In vivo: Animal study showed that the oral administration of RO9021could significanly inhibit the arthritis progression in the mCIA model, with well observed pharmacokinetics-pharmacodynamic correlation [1].
Clinical trial: Up to now, RO9021 is still in the preclinical development stage.
Reference:
[1] Liao C, et al. Selective inhibition of spleen tyrosine kinase (SYK) with a novel orally bioavailable small molecule inhibitor, RO9021, impinges on various innate and adaptive immune responses: implications for SYK inhibitors in autoimmune disease therapy. Arthritis Res Ther. 2013 Oct 4;15(5):R146.
| Cas No. | 1446790-62-0 | SDF | |
| 化学名 | 6-(((1R,2S)-2-aminocyclohexyl)amino)-4-((5,6-dimethylpyridin-2-yl)amino)pyridazine-3-carboxamide | ||
| Canonical SMILES | O=C(C1=NN=C(N[C@H]2[C@@H](N)CCCC2)C=C1NC3=NC(C)=C(C)C=C3)N | ||
| 分子式 | C18H25N7O | 分子量 | 355.44 |
| 溶解度 | Soluble 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 | 2.8134 mL | 14.0671 mL | 28.1341 mL |
| 5 mM | 0.5627 mL | 2.8134 mL | 5.6268 mL |
| 10 mM | 0.2813 mL | 1.4067 mL | 2.8134 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。