MLN8237 (Alisertib) --- Aurora A inhibitor

MLN8237 (Alisertib) is a highly potent and selective Aurora A inhibitor with an IC50 of 1.2 nM, >200-fold selective towards structurally related Aurora B (IC50 of 396.5 nM). It does not have any significant activity against 205 other kinases. MLN8237 treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 treatment also causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM).In recent studies, MLN8237 induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. MLN8237 is currently in Phase II study for treatment of patients with ovarian, fallopian tube, or peritoneal carcinoma.

Product information

CAS Number: 1028486-01-2

Molecular Weight: 518.92

Formula: C27H20ClFN4O4

Synonym:

Alisertib

Chemical Name: 4-((9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl)amino)-2-methoxybenzoic acid

Smiles: COC1=CC(=CC=C1C(O)=O)NC1=NC2=C(CN=C(C3=C(F)C=CC=C3OC)C3=CC(Cl)=CC=C32)C=N1

InChiKey: ZLHFILGSQDJULK-UHFFFAOYSA-N

InChi: InChI=1S/C27H20ClFN4O4/c1-36-21-5-3-4-20(29)23(21)25-19-10-15(28)6-8-17(19)24-14(12-30-25)13-31-27(33-24)32-16-7-9-18(26(34)35)22(11-16)37-2/h3-11,13H,12H2,1-2H3,(H,34,35)(H,31,32,33)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 25 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

MLN8237 was used at 0.5-5 µM concentration in vitro and in cellular assays.

In Vivo:

MLN8237 was dosed to mice orally at 15-30 mg/kg once per day, or in combination with Cisplatin (2 mg/kg) to significantly enhance antitumor activity.

References:

1. Görgün G, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. (2010) Blood. 115(25):5202-13.
2. Kelly KR, et al. The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic myeloid leukaemia and significantly increases the efficacy of nilotinib. (2011) J Cell Mol Med. 15(10):2057-70.
3. Manfredi MG, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. (2011) Clin Cancer Res. 17(24):7614-24.
4. Cervantes A, et al. Phase I pharmacokinetic/pharmacodynamic study of MLN8237, an investigational, oral, selective aurora a kinase inhibitor, in patients with advanced solid tumors. (2012) Clin Cancer Res. 18(17):4764-74.

Products are for research use only. Not for human use.

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