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Formula | C27H20ClFN4O4 |
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Molecular Weight | 518.92 | CAS No. | 1028486-01-2 | |
Solubility (25°C)* | In vitro | DMSO | 100 mg/mL (192.7 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3. | ||
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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 Hexadecadrol, as well as additive effect with doxorubicin and LDP-341. [2] 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 NSC 119875(2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment. [3] |
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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. [2] |
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Features | First orally available inhibitor of Aurora A. |
Kinase Assay: |
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Animal Study: |
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Data from [Oncogene, 2014, 33, 3550-60]
Data from [Data independently produced by EMBO Mol Med, 2013, 5(1), 149-66]
Data from [Data independently produced by Cell Stem Cell, 2012, 11, 179-94]
Data from [EMBO J, 2012, 30, 906-19]
Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] | PubMed: 38310113 |
Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471] | PubMed: 38508142 |
Meningioma achieves malignancy and erastin-induced ferroptosis resistance through FOXM1-AURKA-NRF2 axis [ Redox Biol, 2024, 72:103137] | PubMed: 38642502 |
The Eμ-Ret mouse is a novel model of hyperdiploid B-cell acute lymphoblastic leukemia [ Leukemia, 2024, 38(5):969-980] | PubMed: 38519798 |
AurkA/TPX2 co-overexpression in nontransformed cells promotes genome instability through induction of chromosome mis-segregation and attenuation of the p53 signalling pathway [ Biochim Biophys Acta Mol Basis Dis, 2024, 1870(4):167116] | PubMed: 38447882 |
Spatio-temporal requirements of Aurora kinase A in mouse oocyte meiotic spindle building [ iScience, 2024, 27(8):110451] | PubMed: 39081293 |
Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions [ Sci Rep, 2024, 14(1):4303] | PubMed: 38383756 |
Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma [ Cancer Med, 2024, 13(21):e70082] | PubMed: 39501501 |
Visualization strategies to aid interpretation of high-dimensional genotoxicity data [ Environ Mol Mutagen, 2024, 10.1002/em.22604] | PubMed: 38757760 |
Multiple intersecting pathways are involved in the phosphorylation of CPEB1 to activate translation during mouse oocyte meiosis [ bioRxiv, 2024, 2024.01.17.575938] | PubMed: 38293116 |
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