Hesperadin

HesperadinはオーロラBを有効に抑制して、無細胞試験でIC50値が250 nMになって、AMPK、Lck、MKK1、MAPKAP-K1、CHK1とPHKの活性を著しく下げますが、体内でMKK1活性を抑制しないことです。

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Hesperadin 化学構造
分子量: 516.65

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製品説明

  • Compare Aurora Kinase Inhibitors
    Aurora Kinase製品生物活性の比較
  • 研究分野
  • Hesperadinのメカニズム

製品の説明

生物活性

製品説明 HesperadinはオーロラBを有効に抑制して、無細胞試験でIC50値が250 nMになって、AMPK、Lck、MKK1、MAPKAP-K1、CHK1とPHKの活性を著しく下げますが、体内でMKK1活性を抑制しないことです。
ターゲット 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

プロトコル (参考用のみ)

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]

細胞株 HeLa cells and PtK1 cells
濃度 Final concentration ~500 nM
反応時間 24 and 48 hours
実験の流れ 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)

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 Hesperadin SDF
分子量 516.65
化学式

C29H32N4O3S

CAS No. 422513-13-1
保管 3年-20℃
2年-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 103 mg/mL (199.36 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
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

文献中の引用 (12)

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