Alisertib [1028486-01-2]
Cat# T2241-5mg
Size : 5mg
Brand : TargetMol
Alisertib
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Purity:100%
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COA HPLC HNMR
Alisertib
Catalog No. T2241Cas No. 1028486-01-2
Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B.
All TargetMol products are for research purposes only and cannot be used for human consumption. We do not provide products or services to individuals. Please comply with the intended use and do not use TargetMol products for any other purpose. Pack Size | |
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5 mg | |
10 mg | |
25 mg | |
50 mg | |
100 mg | |
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500 mg | |
1 mL x 10 mM (in DMSO) |
Product Introduction
Bioactivity
Chemical Properties
Storage & Solubility Information
Description | Alisertib (MLN 8237) is a specific Aurora A inhibitor (IC50: 1.2 nM). The selectivity of Alisertib(MLN 8237) is >200-fold higher for Aurora A than Aurora B. |
Targets&IC50 | Aurora A:1.2 nM (cell free) |
In vitro | Treatment of cultured MM cells with Alisertib (MLN8237) results in mitotic spindle abnormalities, mitotic accumulation, as well as inhibition of cell proliferation through apoptosis and senescence. In addition, MLN8237 up-regulates p53 and tumor suppressor genes p21 and p27. Combining MLN8237 with dexamethasone, doxorubicin, or bortezomib induces synergistic/additive anti-MM activity in vitro [1]. Alisertib inhibited AAK over ABK with a selectivity of more than 200-fold in cells. Alisertib inhibited proliferation of human tumor cell lines in vitro [2]. A T217D/W277E double mutant exhibits superior levels of resistance to MLN8237, with the I50 value increasing approximately 20-fold from 30 to 650 nM in the presence of TPX2 [3]. |
In vivo | Tumor burden was significantly reduced and overall survival was significantly increased in animals treated with 30 mg/kg MLN8237 for 21 days. Induction of apoptosis and cell death by MLN8237 were confirmed in tumor cells excised from treated animals by TdT-mediated dUTP nick end labeling assay [1]. Alisertib produced a dose-dependent decrease in bipolar and aligned chromosomes in the HCT-116 xenograft model. Alisertib produced tumor growth inhibition in solid tumor xenograft models and regressions in in vivo lymphoma models. In addition, a dose of alisertib that caused tumor stasis, as measured by volume, resulted in a decrease in FLT uptake [2]. Nude mice bearing human tumor xenografts treated with a single oral dose of alisertib (20 mg/kg) displayed a phenotype consistent with inhibition of Aurora A [4]. |
Kinase Assay | Recombinant murine Aurora A and Aurora B protein were expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A was conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) was assayed in 50 mM Hepes (pH 7.5)/10 mM MgCl2/5 mM DTT/0.05% Tween 20/2 μM peptide substrate/3.3 μCi/ml [γ-33P]ATP at 2 μM by using Image FlashPlates. Aurora B kinase (2 nM) was assayed with 10 μM biotinylated peptide Biotin-TKQTARKSTGGKAPR in 50 mM Tricine (pH 8.0)/2.5 mM MgCl2/5 mM DTT/10% glycerol/2% BSA/40 μCi/ml [γ-33P]ATP at 250 μM. The conditions for all other in vitro kinase assays are available upon request. MLN8054 was run in a 226 kinase screen at a 1 μM compound concentration with an ATP concentration of 10 μM for all assays [2]. |
Cell Research | HCT-116 colorectal carcinoma cells were plated on 6-well dishes (2 × 10^5 per well) and propagated in McCoy's 5A media supplemented with 10% FBS. After 18 hours, alisertib at a final concentration of 0.050, 0.250, or 1.000 μmol/L was added, and the cells were grown for an additional 24 hours. Cells treated with dimethyl sulfoxide (DMSO; 0.2%) served as the untreated vehicle control. The cells were harvested with trypsin EDTA 1×, washed once with PBS, fixed in 70% ethanol, and stored at 4°C for 1 hour. The cells were resuspended in propidium iodide (1:40) and RNAse A (1:5,000) in PBS for 30 minutes at 4°C. Cell-cycle distributions were determined by measuring DNA content using flow cytometry, and samples were analyzed using Winlist 5.0 software [2]. |
Animal Research | Mice were irradiated (200 cGy), and then 5 × 106 MM1.S cells were inoculated subcutaneously in the right flank. When tumor growth was measurable (~ 2 weeks after the injection), mice were assigned into 4 groups (10 mice each) receiving vehicle orally (100 μL of 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) or MLN8237 (7.5 mg/kg, 15 mg/kg, and 30 mg/kg in a final formulation in 10% 2-hydroxypropyl-β-cyclodextrin/1% sodium bicarbonate) for 21 consecutive days. The maximal tolerated dose of MLN8237 in most mouse strains (continuous dosing for 21 days) is approximately 20 mg/kg twice a day (40 mg/kg per day). Tumor volumes were measured by a Vernier caliper every alternate day and calculated using the following formula: length × width2 × 0.5. Tumor growth inhibition (TGI) was calculated using the formula (Δcontrol average volume ? Δtreated average volume) × 100/(Δcontrol average volume). Mice were killed at the end of the treatment, 2 hours after the last treatment, or when tumor reached 2 cm^3; tumors were immediately collected from mice and evaluated for induction of apoptosis and cell death by TdT-mediated dUTP nick end labeling (TUNEL) assay [1]. |
Alias | MLN 8237 |
Molecular Weight | 518.92 |
Formula | C27H20ClFN4O4 |
Cas No. | 1028486-01-2 |
Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. | ||||||||||||||||||||||||||||||
Solubility Information | DMSO: 50 mg/mL (96.35 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) Ethanol: < 1 mg/mL (insoluble or slightly soluble) | ||||||||||||||||||||||||||||||
Solution Preparation Table | |||||||||||||||||||||||||||||||
DMSO
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Please enter your animal experiment information in the following box and click Calculate to obtain the mother liquor preparation method and in vivo formula preparation method:
For example, your dosage is 10 mg/kg Each animal weighs 20 g, and the dosage volume is 100 μL . A total of 10 animals were administered, and the formula you used is 5% DMSO+30% PEG300+5% Tween 80+60% ddH2O. So your working solution concentration is 2 mg/mL。
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Preparation method for in vivo formula: Take 50 μL DMSO main solution, add 300 μLPEG300 mix well and clarify, then add 50 more μL Tween 80, mix well and clarify, then add 600 more μLddH2O mix well and clarify
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Keywords
arrestmyelomaMLN8237cytotoxicityspindleinhibitmitoticAutophagyAurora KinasecancermultipleInhibitorMLN-8237cell-cycleApoptosisAlisertib
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