MLN8237 (Alisertib) (Synonyms: Alisertib) |
| Catalog No.GC12690 |
Alisertib (MLN8237), as an investigational, orally available, selective aurora A kinase inhibitor, is usually used for the treatment of solid tumors and hematologic malignancies.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1028486-01-2
Sample solution is provided at 25 µL, 10mM.
Alisertib (MLN8237), as an investigational, orally available, selective aurora A kinase inhibitor, is usually used for the treatment of solid tumors and hematologic malignancies.[1]
In vitro experiment it shown that treatment with 0.05 μM- 0.5 μM MLN8237 in the leukemia, medulloblastoma, and neuroblastoma cell lines inhibited their cell growth maximumly. However, with >1 μM approximately MLN8237, there was a paradoxical increase in apparent survival in all three lines, most pronounced for Daoy medulloblastoma cell line.[2] In vitro, MLN8237 is effective against both Ewing sarcoma and neuroblastoma cell lines with IC50 of 32 nM and 37 nM, respectively.[4] And alisertib has growth inhibition against U-2 OS cells and MG-63 cells with IC50 of 16.6 μM and 9.5 μM, respectively.[5] In addition, MLN8237 has aggressive inhibition against B-NHL cell proliferation with an IC50 of 10-50 nM and induced apoptosis with a dose- and time-dependent manner.[6]
In vivo, treatment with 30 mg/kg the combination of alisertib and lenvatinib intraperitoneally, every 3 days, for 4 consecutive weeks in BALB/c athymic nude mice, significantly enhanced the antiproliferative and proapoptotic activities, compared with single drugs alone.[3] In vivo efficacy test it indicated that mice were treated with 30 mg/kg MLN8237 for 21 days orally markedly reduced tumor burden and increased overall survival.[7]
References:
[1] Pusalkar S, et al. Biotransformation Pathways and Metabolite Profiles of Oral [14C]Alisertib (MLN8237), an Investigational Aurora A Kinase Inhibitor, in Patients with Advanced Solid Tumors. Drug Metab Dispos. 2020 Mar;48(3):217-229.
[2] Muscal JA, et al. Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. Invest New Drugs. 2013 Feb;31(1):39-45.
[3] Hao J, et al. Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway. Biomed Res Int. 2021 Jul 22;2021:6613439.
[4] Carol H, et al. Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer. Cancer Chemother Pharmacol. 2011 Nov;68(5):1291-304.
[5] Niu NK, et al. Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway. Drug Des Devel Ther. 2015 Mar 12;9:1555-84.
[6] Qi W, et al. Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma. Biochem Pharmacol. 2011 Apr 1;81(7):881-90.
[7] G?rgün G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood. 2010 Jun 24;115(25):5202-13.
| Cell experiment [1]: | |
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Cell lines |
HepG2 and Hep3B cells |
|
Preparation Method |
Treated HepG2 and Hep3B cells with various concentrations of alisertib (7-5000 nM) for 48 hours and concentration-survival curves were plotted. |
|
Reaction Conditions |
7-5000 nM; 48 hours |
|
Applications |
The results clearly showed that alisertib inhibited cell growth in a concentration-dependent manner and cotreated with alisertib significantly enhanced the cytotoxicity of lenvatinib. |
| Animal experiment [2]: | |
|
Animal models |
MCL SCID mouse xenograft model |
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Dosage form |
10 mg/kg and 30 mg/kg; p.o. |
|
Preparation Method |
There were 6 cohorts of 12 mice: vehicle control, MLN8237 at 10 mg/kg and 30 mg/kg PO once a day for 3 weeks, docetaxol at 10 mg/kg IP once/week × 4, MLN8237 at 10 mg/kg or 30 mg/kg for 3 weeks + docetaxel 10 mg/kg once/week × 4. MLN8237 doses were chosen based on prior dose finding studies provided by Millennium Pharmaceuticals, while docetaxel dose was based on a clinically relevant dose in mouse xenograft tumor model. |
|
Applications |
Both combination treatments with docetaxel significantly increased survival over single agent treatments using MLN8237 (10 mg/kg and 30 mg/kg), and high MLN8237 + docetaxel combination treatment increased survival over single agent treatment with docetaxel. |
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References: Hao J, et al. Antitumor Effect of Lenvatinib Combined with Alisertib in Hepatocellular Carcinoma by Targeting the DNA Damage Pathway. Biomed Res Int. 2021 Jul 22;2021:6613439. |
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| Cas No. | 1028486-01-2 | SDF | |
| Synonyms | Alisertib | ||
| Chemical Name | 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid | ||
| Canonical SMILES | COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC | ||
| Formula | C27H20ClFN4O4 | M.Wt | 518.92 |
| Solubility | ≥ 25.9 mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
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- Purity: >99.00%
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