Alisertib(Synonyms: MLN 8237)

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Alisertib (Synonyms: MLN 8237) 纯度: 99.22%

Aliertib (MLN 8237) 是一种口服活性和选择性的 Aurora A 激酶抑制剂 (IC50=1.2 nM)，与Aurora A 激酶结合，导致有丝分裂纺锤体异常、有丝分裂累积。Aliertib (MLN 8237) 通过靶向白血病细胞中的 AKT/mTOR/AMPK/p38 途径诱导其凋亡和自噬。具有抗肿瘤活性。

Alisertib(Synonyms: MLN 8237)

Alisertib Chemical Structure

CAS No. : 1028486-01-2

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10 mM * 1 mL in DMSO ￥799 In-stock
5 mg ￥700 In-stock
10 mg ￥1200 In-stock
50 mg ￥3800 In-stock
100 mg ￥5900 In-stock
200 mg ￥9900 In-stock
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生物活性

Alisertib (MLN 8237) is an orally active and selective Aurora A kinase inhibitor (IC50=1.2 nM), which binds to Aurora A kinase resulting in mitotic spindle abnormalities, mitotic accumulation. Alisertib (MLN 8237) induces apoptosis and autophagy through targeting the AKT/mTOR/AMPK/p38 pathway in leukemic cells. Antitumor activity[1][2][3].

IC50 & Target[3]

Aurora A

1.2 nM (IC50)

Aurora B

396.5 nM (IC50)

体外研究
(In Vitro)

Alisertib (MLN 8237) leads the MM cells to mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. Alisertib up-regulates p53 and tumor suppressor genes p21 and p27[1].
The decreased activity of Alisertib (MLN 8237) for the T217D/W277E Aurora A/TPX2 complex may reflect the increased affinity for ATP induced by cofactor binding to Aurora A[2].
Alisertib (MLN 8237) inhibits cell proliferation with IC50s ranging from 15 to 469 nM in different tumer cell lines[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

Alisertib (MLN 8237) (30 mg/kg, p.o.) significantly reduces tumor burden and increases overall survival in xenograft-murine model of human-MM[1].
Alisertib (3-30 mg/kg; p.o.; once daily for 3 weeks) causes tumor growth inhibition in solid tumor xenograft models[4].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Nude mice bearing HCT-116 colon tumor xenograft[4]
Dosage: 3, 10, or 30 mg/kg
Administration: P.o.; once daily for 3 weeks
Result: Resulted in a dose-dependent TGI (tumor growth inhibition) of 43.3%, 84.2%, and 94.7% for the 3, 10, and 30 mg/kg groups,respectively.

Clinical Trial

分子量

518.92

Formula

C27H20ClFN4O4
CAS 号

1028486-01-2
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 25 mg/mL (48.18 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.9271 mL 9.6354 mL 19.2708 mL
5 mM 0.3854 mL 1.9271 mL 3.8542 mL
10 mM 0.1927 mL 0.9635 mL 1.9271 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: 2.08 mg/mL (4.01 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.08 mg/mL (4.01 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: 2.08 mg/mL (4.01 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.08 mg/mL (4.01 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (4.01 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (4.01 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 MCE 网站选购。
参考文献

  • [1]. Güllü G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma Blood June 24, 2010 vol. 115 no. 25 5202-5213.

    [2]. Sloane DA, et al. Drug-Resistant Aurora A Mutants for Cellular Target Validation of the Small Molecule Kinase Inhibitors MLN8054 and MLN8237 ACS Chem. Biol., 2010, 5 (6), pp 563-576.

    [3]. Bavetsias V, et al. Aurora Kinase Inhibitors: Current Status and Outlook. Front Oncol. 2015 Dec 21;5:278.

    [4]. Manfredi MG, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays.Clin Cancer Res. 2011 Dec 15;17(24):7614-7624.