| Identification | Back Directory | [Name]
Alisertib (MLN8237) | [CAS]
1028486-01-2 | [Synonyms]
MLN-8237
Alisertib
Alisertib (MLN8237)
MLN8237 (Alisertib)
MLN 8237 (Contain 10% DMSO)
alisertib (auroura A kinase inhibitor)
4-((9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-benzo[c]pyrimido-[4,5-e]azepin-2-yl)amino)-2-methoxy
4-[[9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid
4-((9-chloro-7-(2-fluoro-6-Methoxyphenyl)-5H-benzo[c]pyriMido[4,5-e]azepin-2-yl)aMino)-2-Methoxybenzoic acid
Benzoic acid, 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxy-
MLN-8237 4-[[9-Chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid | [EINECS(EC#)]
1592732-453-0 | [Molecular Formula]
C27H20ClFN4O4 | [MDL Number]
MFCD16621243 | [MOL File]
1028486-01-2.mol | [Molecular Weight]
518.924 |
| Chemical Properties | Back Directory | [Boiling point ]
729.1±70.0 °C(Predicted) | [density ]
1.43±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (up to 5 mg/ml) | [form ]
solid | [pka]
4.07±0.10(Predicted) | [color ]
Off-white | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Chemical Properties]
Off-White Solid | [Usage]
An Aurora kinase inhibitor, used to treat patients with advanced solid tumors. | [Uses]
An Aurora kinase inhibitor, used to treat patients with advanced solid tumors. | [Definition]
ChEBI: 4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid is a benzazepine. | [target]
Aurora A | [References]
1) Sells?et al.?(2015),?MLN8054 and Alisertib (MLN8237):Discovery of Selective Oral Aurora A Inhibitors; ACS Med. Chem. Lett.?6?630
2) Richards?et al.?(2016),?Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors; Proc. Natl. Acad. Sci. USA?113?13726
3) Brockmann?et al.?(2013),?Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma; Cancer Cell?24?75
4) Dauch?et al.?(2016),?A MYC-aurora kinase A protein complex represents an actionable drug target in p53-altered liver cancer; Nat. Med.?22?744
5) Li?et al.?(2015),?The investigational Aurora kinase A inhibitor alisertib (MLN8237) induces cell cycle G2/M arrest, apoptosis, and autophagy via p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells; Drug Des. Devel. Ther.?16?1627
6) Shang?et al.?(2017),?Alisertib promotes apoptosis and autophagy in melanoma through p38 MAPK-mediated aurora a signaling; Oncotarget?8?107076 |
| Questions And Answer | Back Directory | [Description]
Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3. | [In vitro]
MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. [1] MLN8237 (0.5 μM) 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 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib.MLN8237 (0.5 μM) treatment 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), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment. | [In vivo]
MLN8237 significantly reduces the tumor burden with tumor growth inhibition (TGI) of 42% and 80% at 15 mg/kg and 30 mg/kg, respectively, and prolongs the survival of mice compared with the control. |
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