Hesperadin

HesperadinはオーロラBキナーゼの阻害剤で、人間のオーロラBとT. bruceiオーロラ・キナーゼ-1(TbAUK1)に作用すると、 IC50がそれぞれ 250 nM 、40 nM になる。

目録号S1529
5 5 5レビュー 6製品表彰状
価格 在庫  
USD 214 In stock
USD 403 In stock
USD 441 In stock
USD 1222 In stock

Hesperadin 化学構造
分子量: 516.65

品質と確認

カスタマーレビュー(5)

Quality Control & MSDS

製品情報

  • Compare Aurora Kinase Inhibitors
    Aurora Kinase阻害剤を比較
  • 研究分野
  • Hesperadinのメカニズム

製品の説明

生物活性

情報 HesperadinはオーロラBキナーゼの阻害剤で、人間のオーロラBとT. bruceiオーロラ・キナーゼ-1(TbAUK1)に作用すると、 IC50がそれぞれ 250 nM 、40 nM になる。
目標 Aurora B (human) TbAUK1
IC50 250 nM [1] 40 nM [2]
In vitro試験 Hesperadin inhibits the ability of immunoprecipitated Aurora B to phosphorylate histone H3 with IC50 of 250 nM and markedly reduces the activity of other kinases (AMPK, Lck, MKK1, MAPKAP-K1, CHK1, and PHK) at a concentration of 1 μM. In contrast, only 20-100 nM of Hesperadin is sufficient to induce the loss of mitotic histone H3-Ser10 phosphorylation in HeLa cells. Hesperadin treatment causes defects in mitosis and cytokinesis, leading to stoppage of proliferation of HeLa cells and polyploidization, which can be specifically ascribed to the inhibition of Aurora B function during the process of chromosome attachment. Hesperadin (100 nM) quickly overrides the mitotic arrest induced by taxol or monastrol but not by nocodazole. Hesperadin and nocodazole treatment in HeLa cells abolishes kinetochore localization of BubR1 and diminishes the intensity of Bub1 at kinetochores, suggesting that Aurora B function is required for efficient kinetochore recruitment of BubR1 and Bub1, which in turn might be necessary for prolonged checkpoint signaling. [1] Hesperadin prevents the phosphorylation of recombinant trypanosome histone H3 by the T. brucei Aurora kinase-1 (TbAUK1) from pathogenic Trypanosoma brucei with IC50 of 40 nM in vitro kinase assays. Hesperadin significantly inhibits cell growth of cultured infectious bloodstream forms (BF) with IC50 of 48 nM, and only weakly inhibits cell growth of insect stage procyclic forms (PF) with IC50 of 550 nM. [2]
In vivo試験
臨床試験
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]

The Aurora B kinase assay For the Aurora B kinase assay, HeLa cells are lysed in a buffer containing 50 mM NaCl. The whole cell extract is spun at 13,000 rpm for 20 minutes at 4 °C using a table top centrifuge. The pellet obtained from 200 mg of whole cell extract is extracted again in 15 mL lysis buffer containing 250 mM NaCl in order to obtain active Aurora B kinase from mitotic chromatin. The low speed supernatant of the latter extract is used for immunoprecipitation. Monoclonal mouse anti–AIM-1, or mouse anti-HA, is coupled to GammaBind Plus Sepharose, and beads are rotated over-end in the extract for 90 minutes at 4 °C. Beads are washed, aliquoted, and washed in kinase buffer (20 mM Tris, pH 7.5, 150 mM NaCl, 10 mM MgCl2, 1 mM DTT, 10 mM NaF). The kinase assay is performed with 10 μL beads in 20 μL kinase buffer containing 5 μg histone H3, 10 μM ATP, 2.5 μCi [γ-32P]ATP, and different concentrations of Hesperadin for 20 minutes at 37 °C. SDS sample buffer is added, and samples are boiled and resolved by SDS-PAGE. The gel is dried, and the radioactive signal is detected by PhosphorImager analysis. The data is analyzed using ImageQuant software.

細胞アッセイ: [1]

細胞系 HeLa cells and PtK1 cells
濃度 Final concentration ~500 nM
処理時間 24 and 48 hours
方法 Cells are exposed to different concentrations of Hesperadin for 24 and 48 hours. At indicated time points, methanol-fixed cell samples are washed with PBS and subsequently stained in PI buffer (50 μg/mL propidium iodide, 10 mM Tris, pH 7.5, 5 mM MgCl2, 200 μg/mL RNase A) for 20-40 minutes at 37 °C. The DNA content is determined by flow cytometry.

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 Hesperadin SDF
分子量 516.65
化学式

C29H32N4O3S

CAS No. 422513-13-1
保管 2年-20℃
6月-80℃in DMSO
別名
溶解度 (25°C) * In vitro DMSO 103 mg/mL (199 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
In vivo 30% PEG400/0.5% Tween80/5% propylene glycol 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 (Z)-N-(2-oxo-3-(phenyl(4-(piperidin-1-ylmethyl)phenylamino)methylene)indolin-5-yl)ethanesulfonamide

研究分野

カスタマーレビュー (5)


Click to enlarge
Rating
Source Nat Commun , 2011, 2, 316. Hesperadin purchased from Selleck
Method Live cell imaging, immunfluorescence
Cell Lines HeLa cells
Concentrations 100 nM
Incubation Time 2 h
Results Aurora B inhibition using the small molecules Hesperadin or ZM447439 reduced Mps1 kinetochore binding throughout mitosis.

Click to enlarge
Rating
Source Nat Commun , 2011, 2, 316 . Hesperadin purchased from Selleck
Method Time-lapse analysis
Cell Lines U2OS cells
Concentrations
Incubation Time 0-400 min
Results The fast mitotic exit in nocodazole induced by Hec1 depletion combined with ZM447439 or Hesperadin treatment was prevented by Mis12–Mps1∆200 expression

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. Hesperadin purchased from Selleck
Method Western blot
Cell Lines
Concentrations 0-10 μM
Incubation Time
Results Hesperadin treatment resulted in a reduction of Histone phosphorylation.

Click to enlarge
Rating
Source Hesperadin purchased from Selleck
Method Cdk1 reactivation assay
Cell Lines U2OS cell
Concentrations 125 nM
Incubation Time 25 min
Results

Click to enlarge
Rating
Source Hesperadin purchased from Selleck
Method Immunofluorescence microscopy
Cell Lines HeLa cells
Concentrations 50 nM
Incubation Time 75 min
Results all three Haspin inhibitors substantially reduced CENP-AS7ph in nocodazole-treated cells, and this loss could be rescued by forced targeting of Aurora B to centromeres with CENP-B–INCENP.

製品表彰状 (6)

技術サポート&よくある質問(FAQ)

顧客がするかもしれない質問に対する答えは、指示を取り扱っている阻害剤で見つかります。話題は、貯蔵液(阻害剤と特別な注意を細胞ベースの分析法と動物のために必要とする問題を保存することは実験します)を準備する方法を含みます。

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)

他の問い合わせをするならば、メッセージを残してください。

* 必須

Related オーロラ・キナーゼ 阻害剤

  • MK-8745

    MK-8745 is a potent and selective Aurora A inhibitor with IC50 of 0.6 nM, more than 450-fold selectivity for Aurora A over Aurora B.

  • LEE011

    LEE011 is an orally available, and highly specific CDK4/6 inhibitor.

  • K-Ras(G12C) inhibitor 6

    K-Ras(G12C) inhibitor 6 is an allosteric, and selective inhibitor of oncogenic K-Ras(G12C).

  • EHop-016

    EHop-016 is a specific Rac GTPase inhibitor with IC50 of 1.1 μM for Rac1, equally potent inhibition for Rac3.

  • Alisertib (MLN8237)

    Alisertib (MLN8237)は、1.2nMのIC50による選択的なオーロラA阻害剤です。

    Features:MLN8237 是第一个口服有效的小分子Aurora A激酶选择性抑制剂。

  • VX-680 (Tozasertib, MK-0457)

    VX-680 (Tozasertib, MK-0457)は汎オーロラ・キナーゼ(AK)阻害剤、、オーロラA、オーロラBとオーロラCに作用すると、 Kiapp がそれぞれ 0.6 nM、18 nM 、 4.6 nMになる。

  • Barasertib (AZD1152-HQPA)

    Barasertib (AZD1152-HQPA)は、0.37nMのIC50による非常に選択的なオーロラB阻害剤です。

  • ZM 447439

    ZM 447439は、オーロラ選択ATPです-競争的な阻害剤で、オーロラAキナーゼとオーロラBキナーゼに作用すると、IC50が それぞれ 110 nM と 130 nM,になる。

    Features:ZM-447439是Aurora选择性ATP竞争性抑制剂

  • MLN8054

    MLN8054は、4nMのIC50によるオーロラAキナーゼの強力で選択的な阻害剤です。

    Features:MLN8054是有效的 Aurora A激酶选择性抑制剂。

  • Aurora A Inhibitor I

    Aurora A Inhibitor I阻害剤IはAurora A選択阻害剤、IC50が3.4nM。

    Features:Aurora A Inhibitor I 是2,4-二苯胺嘧啶抑制剂。

最近見られたアイテム

Tags: Hesperadinを買う | Hesperadin供給者 | Hesperadinを購入する | Hesperadin費用 | Hesperadin生産者 | オーダーHesperadin | Hesperadin代理店
お問い合わせ