Cat. No. Name Size Price Add Cart
KI0222MLN82375 mg$192
MLN823710 mg$336
MLN823750 mg$1072
MLN8237200 mg$2832

Chemical Characteristic

Product NameMLN8237
SynonymsAlisertib
CAS No.1028486-01-2
Molecular Weight 518.92
FormulaC27H20ClFN4O4
Chemical NameBenzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-
SmilesC(=O)(c1c(cc(cc1)Nc1nc2c(CN=C(c3c2ccc(c3)Cl)c2c(cccc2OC)F)cn1)OC)O
Chemical Structure
DocumentsHPLC MS COA

Biological activities

MLN8237 is a selective Aurora A and Aurora B inhibitor with IC50 values of 1.2 and 396.5 nM, respectively. MLN8237 is at least 200-fold more selective for Aurora A (IC50= 6.7 nM) than Aurora B (IC50= 1.5 µM) according to cell-based assays. At a concentration of 50 nM MLN8237, cell-cycle analysis shows an increase in cells in the G2/M phase at 24 and 48 hours. At concentrations of 50 nM, 250 nM and 1 µM MLN8237, cell-cycle analysis also shows an increase in the number of cells with 8N DNA content. MLN8237 inhibits cell proliferation with IC50 values ranging from 15 to 469 nM in a broad panel of adherent and suspended cell lines.[1] HCT-116 cells with MLN8054 at 0.25, 1, and 4µM inhibits Aurora A autophosphorylation on T288. In mitotic HeLa cells, MLN8054 inhibits Aurora A in 1 hour with an average IC50 of 34 nM. In both HCT-116 colorectal and PC-3 prostate human tumor cells, treatment with 1 µM MLN8054 induces increased 4N cells relative to control cells. MLN8054 effectively inhibits the growth of various cell lines (HCT-116, SW480, DLD-1, MCF-7, MDA-MB-231, Calu-6, H460, SKOV-3 and PC-3) with IC50 values ranging from 0.11 to 1.43 µM.[2] In MM1.S and OPM1 MM cells, MLN8237 (0.5 µM) decreases phosphorylation of Aurora-A kinase. MLN8237 (0.1 nM-4 µM) induces inhibition of cell viability (40%-60%) and proliferation (70%-90%) in dexamethasone-resistant (MM.1R), melphalan-resistant (LR5), and doxorubicin-resistant (RPMI-DOX40) MM cells. Furthermore, costaining with annexin V and PI shows signi?cant induction of apoptosis by MLN8237 treatment (0.5-1 µM) in both MM cell lines (RPMI8226 and OPM1) and primary tumor cells as early as 24 hours. MLN8237 (0.5 µM) also induces cleavage of PARP, caspase 9, and caspase 3 in MM cell lines MM1S and OPM1.[3] In HCT-116 xenografts model, MLN8237 (orally at 3, 10, and 30 mg/kg) increases mitotic index, reduces bipolar mitotic spindles, and increases chromosome alignment abnormalities. In nude mice bearing subcutaneous HCT-116 tumors, MLN8237 treatment results in a dose-dependent tumor growth inhibition (TGI) of 43.3%, 84.2%, and 94.7% for the 3, 10, and 30 mg/kg groups, respectively. All doses of MLN8237 are well tolerated with the maximum body weight loss of 7.4% in the 30 mg/kg group. In the non-Hodgkin?? lymphoma model OCI-LY19, MLN8237 (either 20 mg/kg twice daily or 30 mg/kg once daily) results in a reduction in luminescent signal below baseline and a TGI of 106% for both groups. Moreover, tumors in the 20 mg/kg dose MLN8237 group do not grow back after more than 60 days of monitoring. Furthermore, MLN8237 shows broad antitumor activity across a diverse set of xenograft models, with TGI of greater than 76% at 30 mg/kg in all models tested.[1]

Protocols

MLN8054 is formulated in 10% 2-hydroxypropyl-b-cyclodextrin and 1% sodium bicarbonate .[1]

References

[1] 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, 17(24): 7614-7624.
[2] Tomita M, et al. Aurora A selective inhibitor MLN8237 suppresses the growth and survival of HTLV-1-infected T-cells in vitro. Cancer Sci. 2010,101(5): 1204-1211.
[3] G?rg?n G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood. 2010, 115(25): 5202-5213.

Please click here to fill online order form, and we will make sure to supply you product with detail information. This process usually takes between 24 to 48 hours, depending on products stock avaliability. All inquires and subsequent projects are handled in the strictest confidence and will be backed by a confidentiality agreement if required.
KareBayTM provides scientists and clinicians with a wide range of biotechnological products and science lab supplies for chemical research and analyzing life processes. KareBay's extensive capabilities include commercializing reagents and kits, manufacturing biotech products and providing contract research services to organizations worldwide. Our many global labs, offices, and business partners enable KareBay to extend its products and services to its customer base around the world.

Our products are used for research, laboratory and further evaluation purposes. They are not for human use.