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

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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 mM)
95 mg/mL (200 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

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.

製品表彰状 (4)

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