Rigosertib
(Synonyms: 瑞格色替; ON-01910) 目录号 : GC12415
Rigosertib (ON-01910) 是一种多激酶抑制剂和选择性抗癌剂，通过抑制 PI3 激酶/Akt 通路诱导细胞凋亡，促进组蛋白 H2AX 的磷酸化并诱导细胞周期 G2/M 停滞。 Rigosertib 是一种选择性和非 ATP 竞争性的 PLK1 抑制剂，IC50 为 9 nM。
Cas No.:592542-59-1
Sample solution is provided at 25 µL, 10mM.
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Rigosertib is a dual inhibitor of phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (PLK1) [1].
In vitro studies show that rigosertib inhibits the PI3K/AKT pathway, down-regulates cyclin D1, induces NOXA and BIM and activates the JNK pathway in human leukemic cells. Rigosertib induces apoptosis of a variety of human tumor cell lines including breast, prostate, ovarian, pancreatic, SCLC, colorectal, melanoma and et al. For instant, it shows anti-tumor efficacy in BT20, MCF-7, BT474, OV-CAR-3, A549 and HCT-116 with IC50 values of 80nM, 75nM, 50nM, 75nM, 90nM and 75nM, respectively. In addition, rigosertib is also effective against the drug resistant tumor cell lines. It potently inhibits tumor growth with IC50 values of 100nM and 50nM against MES-SA/DX5 and CEM/C2, respectively. Moreover, it is reported that rigosertib can affect the cell cycle of both normal cells and tumor cells. Rigosertib leads to a blockade of cell cycle progression in the G1 and G2/M phases in normal diploid human fetal lung cells. When treated with DU145 cells, rigosertib induces cell cycle arrest in G2/M phase [2].
References:
[1] Anderson R T, Keysar S B, Bowles D W, et al. The Dual Pathway Inhibitor Rigosertib Is Effective in Direct Patient Tumor Xenografts of Head and Neck Squamous Cell Carcinomas. Molecular cancer therapeutics, 2013, 12(10): 1994-2005.
[2] Reddy M V R, Venkatapuram P, Mallireddigari M R, et al. Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-Methoxy-5-[(2′, 4′, 6′-trimethoxystyrylsulfonyl) methyl] phenylamino} acetate (ON 01910. Na): synthesis, structure–activity relationship, and biological activity. Journal of medicinal chemistry, 2011, 54(18): 6254-6276.
Kinase experiment: | Recombinant PLK1 (10 ng) is incubated with different concentrations of Rigosertib in a 15 µL reaction mixture (50 mM HEPES, 10 mM MgCl2, 1 mM EDTA, 2 mM Dithiothreitol, 0.01% NP-40 [pH 7.5]) for 30 min at room temperature. Kinase reactions are performed for 20 min at 30°C in a volume of 20 µL (15 µL enzyme + inhibitor, 2 µL 1 mM ATP), 2 µL of γ32P-ATP (40 μCi), and 1 µL of recombinant Cdc25C (100 ng) or casein (1 μg) substrates. Reactions are terminated by boiling for 2 min in 20 µL of 2× Laemmli buffer. Phosphorylated substrates are separated by 18% SDS-PAGE. The gels are dried and exposed to X-ray film for 3-10 min. |
Cell experiment: | Tumor cells are plated into six-well dishes at a density of 1×105 cells/mL/well, and Rigosertib is added 24 hours later at various concentrations. Cell counts are determined from duplicate wells after 96-hour of treatment. The total number of viable cells is determined by trypan blue exclusion. |
Animal experiment: | Bel-7402 tumor models: twenty female athymic (NCR-nu/nu) nude mice are injected with 1 × 107 Bel-7402 tumor cells subcutaneously, and 10-14 days later, when the tumor volumes reach 200-250 mm, the mice are divided into four groups such that each group harbors tumors of the same volume. Rigosertib (ON01910, 250 mg/kg) dissolved in PBS is administered alone or in combination with NSC 266046 (100 mg/kg) intraperitonially on alternate days. Tumor measurements are done two times/week using traceable digital vernier calipers. Body weight is determined during each measurement. The animals are observed for signs of toxicity[1]. |
References: [1]. Xu F, et al. Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signalingtransduction pathways in high-grade myelodysplastic syndrome. Sci Rep. 2014 Dec 4;4:7310. | |
| Cas No. | 592542-59-1 | SDF | |
| 别名 | 瑞格色替; ON-01910 | ||
| 化学名 | 2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid | ||
| Canonical SMILES | COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)O | ||
| 分子式 | C21H25NO8S | 分子量 | 451.49 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C,unstable in solution, ready to use. |
| 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 | 2.2149 mL | 11.0744 mL | 22.1489 mL |
| 5 mM | 0.443 mL | 2.2149 mL | 4.4298 mL |
| 10 mM | 0.2215 mL | 1.1074 mL | 2.2149 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: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet