Alisertib (MLN8237)

製品コードS1133 バッチS113314

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₇H₂₀ClFN₄O₄
	分子量	518.92	CAS No.	1028486-01-2
Solubility (25°C)*	体外	DMSO	33 mg/mL (63.59 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
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]
特徴	First orally available inhibitor of Aurora A.

プロトコル(参考用のみ)

キナーゼアッセイ	Aurora A radioactive Flashplate enzyme assay
キナーゼアッセイ	Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl₂, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-³³P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates.
細胞アッセイ	細胞株	MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	24, 48, and 72 hours
	実験の流れ	Cells are exposed to various concentrations of MLN8237 for 24, 48, and 72 hours. Cells viability is measured using MTT assay, and cell proliferation is measured using ³[H]-thymidine incorporation. For cell cycle analysis, cells are permeabilized by 70% ethanol at -20 °C, and incubated with 50 μg/mL PI and 20 units/mL RNase-A. DNA content is analyzed by flow cytometry using BDFACS-Canto II and FlowJo software. For the detection of apoptosis and senescence, cells are stained with Resorcinolphthalein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software.
動物実験	動物モデル	Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells
	投薬量	~30 mg/kg/day
	投与方法	Orally

参考

カスタマーフィードバック

: 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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Aurora Kinase A Inhibition Potentiates Platinum and Radiation Cytotoxicity in Non-Small-Cell Lung Cancer Cells and Induces Expression of Alternative Immune Checkpoints [ Cancers (Basel), 2024, 16(16)2805]	PubMed: 39199578
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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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