Rigosertib (ON-01910) 化学構造
分子量: 473.47

高品質保証

カスタマーフィードバック(3)

Quality Control & MSDS

製品説明

  • Compare PLK Inhibitors
    PLK製品生物活性の比較
  • 研究分野

製品の説明

生物活性

製品説明 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。
ターゲット 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

プロトコル (参考用のみ)

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]

細胞株 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.
反応時間 96 hours
実験の流れ 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
投与方法 Intraperitonially

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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 solvent
別名 N/A
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)

カスタマーフィードバック (3)


Click to enlarge
Rating
Source PLoS One, 2013, 8(11), e79863. Rigosertib (ON-01910) purchased from Selleck
Method Western blot
Cell Lines LCL, HT, SU-DHL-5 cells
Concentrations 0-0.5 uM
Incubation Time
Results Along with cell death, immunoblotting demonstrated that ON 01910.Na induced hyperphosphorylation of RanGAP1, increased expression of RanGAP1.SUMO1 but decreased expression of free unmodified RanGAP1.

Click to enlarge
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.

文献中の引用 (5)

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

電話番号: +1-832-582-8158 Ext:3月曜日〜金曜日 9:00 AM–5:00 PM (米国中部標準時)

他の質問がある場合は、お気軽くお問合せください。

* 必須

Related PLK 阻害剤

  • NMS-P937 (NMS1286937)

    NMS-P937 (NMS1286937) is an orally available, selective Polo-like Kinase 1 (PLK1) inhibitor with IC50 of 2 nM, 5000-fold selectivity over PLK2/PLK3. Phase 1.

  • SBE 13 HCl

    SBE 13 HCl is a potent and selective PLK1 inhibitor with IC50 of 200 pM, >4000-fold selectivity over Aurora A kinase, Plk2 and Plk3.

  • Ro-3306

    RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.

  • K-Ras(G12C) inhibitor 12

    K-Ras(G12C) inhibitor 12 is an allosteric inhibitor of oncogenic K-Ras(G12C).

  • BI 2536

    BI2536は、0.83nMのIC50による強力なポロのようなキナーゼ1(Plk1)阻害剤です。

    Features:The first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition.

  • HMN-214

    HMN-214はポロのようなキナーゼ(Plk)1への経口で強力な阻害剤で、IC50が118 nMになる。

  • GSK461364

    GSK461364はチオフェンアミド、PLK1酵素の阻害で、Kiが2 nM。[1]

    Features:Demonstrates >390-fold selectivity for Plk1 relative to Plk2 and Plk3.

  • Volasertib (BI 6727)

    Volasertib (BI 6727)は、0.87nMのIC50による非常に強力なポロのようなキナーゼ1(Plk1)阻害剤です。

    Features:A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.

  • MLN0905

    MLN0905は有効的なPLK1阻害剤で、IC50が2 nMです。

最近チェックしたアイテム

Tags: Rigosertib (ON-01910)を買う | Rigosertib (ON-01910)供給者 | Rigosertib (ON-01910)を購入する | Rigosertib (ON-01910)費用 | Rigosertib (ON-01910)生産者 | オーダーRigosertib (ON-01910) | Rigosertib (ON-01910)代理店
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description
お問い合わせ