Rigosertib (ON-01910)

Rigosertib (ON-01910)はどんな作用にPoloキナーゼ(PLK1)の非ATP競争性阻害剤、IC50が9nMになる。

目録号S1362
5 5 2レビュー 4製品表彰状
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Rigosertib (ON-01910) 化学構造
分子量: 473.47

品質と確認

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Quality Control & MSDS

製品情報

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  • 研究分野

製品の説明

生物活性

情報 Rigosertib (ON-01910)はどんな作用にPoloキナーゼ(PLK1)の非ATP競争性阻害剤、IC50が9nMになる。
目標 PLK1
IC50 9 nM [1]
In vitro試験 Rigosertib is non-ATP-competitive inhibitor to PLK1 with IC50 of 9 nM. Rigosertib also exhibits inhibition against PLK2, PDGFR, Flt1, BCR-ABL, Fyn, Src, and CDK1, with IC50 of 18-260 nM. Rigosertib shows cell killing activity against 94 different tumor cell lines with IC50 of 50-250 nM, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. While in normal cells, such as HFL, PrEC, HMEC, and HUVEC, Rigosertib has little or no effect unless its concentration is greater than 5-10 μM. In HeLa cells, Rigosertib (100-250 nM) induces spindle abnormalities and apoptosis. [1] Rigosertib also inhibits several multidrug resistant tumor cell lines, including MES-SA, MES-SA/DX5a, CEM, and CEM/C2a, with IC50 of 50-100 nM. In DU145 cells, Rigosertib (0.25-5 μM) blocks cell cycle progression in G2/M phase, results in an accumulation of cells containing subG1 content of DNA, and activates apoptotic pathways. In A549 cells, Rigosertib (50 nM-0.5 μM) induces loss of viability and caspase 3/7 activation. [2] In a recent study, Rigosertib induces apoptosis in chronic lymphocytic leukemia (CLL) cells without toxicity against T-cells or normal B-cells. Rigosertib also abrogates the pro-survival effect of follicular dendritic cells on CLL cells and reduces SDF-1-induced migration of leukemic cells. [3]
In vivo試験 In mouse xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells, Rigosertib (250 mg/kg) markedly inhibits tumor growth. [1] Rigosertib (200 mg/kg) shows inhibition on tumor growth in a mouse xengraft model of BT20 cells. [2]
臨床試験 Rigosertib is currently under a Phase III clinical trial in refractory myelodysplastic syndrome patients with excess blasts.
特集

推薦された実験操作 (公開の文献だけ)

キナーゼアッセイ: [1]

In vitro enzyme assays for PLK1 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.

細胞アッセイ: [2]

細胞系 A number of tumor cell lines, including BT20, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, HeLa, and Raji cells
濃度 1 nM - 10 μM, dissolved in DMSO as stock solution.
処理時間 96 hours
方法 Cells are grown in either DMEM or RPMI supplemented with 10% fetal bovine serum and 1 unit/mL penicillin-streptomycin solution. Tumor cells are plated into six-well dishes at a density of 1 × 105cells/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 exclusio

動物実験: [1]

動物モデル Mouse (female athymic, NCR-nu/nu) xenograft models of Bel-7402, MCF-7, and MIA-PaCa cells
製剤 Dissolved in PBS
投薬量 250 mg/kg
管理 Intraperitonially
Solubility Saline 30 mg/mL
* 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesBaboonDogMonkeyRabbitGuinea pigRatHamsterMouse
Weight (kg)121031.80.40.150.080.02
Body Surface Area (m2)0.60.50.240.150.050.0250.020.007
Km factor202012128653
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Rigosertib (ON-01910) SDF
分子量 473.47
化学式

C21H24NNaO8S

CAS No. 1225497-78-8
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 95 mg/mL (200.64 mM)
95 mg/mL (200.64 mM)
エタノール <1 mg/mL (<1 mM)
In vivo Saline 30 mg/mL
* <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.
化学名 N-​[2-​methoxy-​5-​[[[2-​(2,​4,​6-​trimethoxyphenyl)​ethenyl]​sulfonyl]​methyl]​phenyl]​-​glycine,sodium salt (1:1)

研究分野

カスタマーレビュー (2)


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Rating
Source Rigosertib (ON-01910) purchased from Selleck
Method MTT Assay
Cell Lines leukemia cell lines
Concentrations 0.001-1 μM
Incubation Time 48 h
Results ON01910 demonstrated a good capacity to inhibit leukemia cell growth in a concentration dependent manner.

Click to enlarge
Rating
Source Dr. Antonino Maria Sparta, PhD University of Bologna. Rigosertib (ON-01910) purchased from Selleck
Method Western Blot
Cell Lines Jurkat E6.1 Cells
Concentrations 500 nM
Incubation Time 48 h
Results Both CCT137690 and ON01910 were significantly able to reduce the phosphorylation states of the centrosomal protein TACC3 and of the histone H3, which are known targets of Aurora kinases.

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