MLN8237 (Alisertib) (Synonyms: Alisertib) |
Catalog No.GC12690 |
An Aurora A kinase inhibitor
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.
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