ZM 447439

製品コードS1103 バッチS110301

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	C₂₉H₃₁N₅O₄
	分子量	513.59	CAS No.	331771-20-1
Solubility (25°C)*	体外	DMSO	103 mg/mL (200.54 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	ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.
in vitro	In vitro, ZM-447439 selectively inhibits recombinant human Aurora A and B with IC50 values of 110 and 130 nM, respectively, while other protein kinases of diverse structural types including the mitotic kinases CDK1 and PLK1 are inhibited with IC50 values >10 μM. ^[1] Aurora kinase inhibitor, ZM-447439 time- and dose-dependently inhibits the growth of all three cell lines with IC50 values of 3 μM (BON), 0.9 μM (QGP-1) and 3 μM (MIP-101) after 72 hours of continuous exposure. In addition, ZM-447439 potently induces cell apoptosis by promoting DNA fragmentation and caspase 3 and 7 activation, and arrests GEP-NET cells in the G₀ /G₁and G₂/M phase of the cell cycle. ^[2] In mouse embryo, inhibition of Aurora kinase activity by ZM-447439 results in abnormalities during mitosis by regulating the phosphorylation of histone H3 serine 10 (H3S10Ph) from G2 to metaphase with different perturbations in each embryonic cycle. ^[3] A recent study shows that ZM-447439 exhibits growth inhibitory and proapoptotic effect on cervical cancer SiHa cells, and enhances the chemosensitivity to cisplatin. ^[4]
特徴	An Aurora selective ATP-competitive inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase assays
キナーゼアッセイ	Recombinant Aurora A and B are expressed as NH₂-terminal His₆-tagged fusion proteins using a baculovirus expression system. Aurora A is purified by affinity chromatography using Ni-NTA agarose, and Aurora B is purified by ion exchange chromatography using CM Sepharose Fast Flow. 1 ng purified recombinant enzyme is added to a reaction cocktail containing 25 mM Tris-HCl, pH 7.5, 12.5 mM KCl, 2.5 mM NaF, 0.6 mM DTT, 6.25 mM MnCl₂, 10 μM peptide substrate, 10 μM for Aurora A or 5 μM ATP for Aurora B, and 0.2 μCi γ-[³³P]ATP (specific activity ≥2,500 Ci/mmol), and is then incubated at RT for 60 minutes. Reactions are stopped by addition of 20% phosphoric acid, and the products are captured on P30 nitrocellulose filters and assayed for incorporation of ³³P with a Betaplate^TM counter. No enzyme and no compound control values are used to determine the concentration of ZM447439, which gave 50% inhibition of enzyme activity. Further details are available on request from Nicholas Keen.
細胞アッセイ	細胞株	BON, QGP-1 and MIP-101 cells
	濃度	0-5 μM
	反応時間	72 hours
	実験の流れ	Cell number is evaluated by crystal violet staining. In brief, cells in 96-well plates are fixed with 1% glutaraldehyde. Then cells are stained with 0.1% crystal violet. The unbound dye is removed by washing with water. Bound crystal violet is solubilized with 0.2% Triton X-100. Light extinction which increases linearly with the cell number is analyzed at 570 nm using an ELISA reader.

参考

[4] Zhang L, et al. J Obstet Gynaecol Res. 2011, 37(6), 591-600.

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カスタマーフィードバック

: Data from [Mol Biol Cell, 2011, 22, 4227-35]

: , , Dr. Yuanhong Chen of University of Nebraska

: , , Dr. Zhang of Tianjin Medical University

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
Human Endonuclease ANKLE1 Localizes at the Midbody and Processes Chromatin Bridges to Prevent DNA Damage and cGAS-STING Activation [ Adv Sci (Weinh), 2023, 10(12):e2204388]	PubMed: 36825683
Extra centrosomes induce PIDD1-mediated inflammation and immunosurveillance [ EMBO J, 2023, e113510.]	PubMed: 37530438
RIF1 suppresses the formation of single-stranded ultrafine anaphase bridges via protein phosphatase 1 [ Cell Rep, 2023, 42(2):112032]	PubMed: 36719798
Aberrant metabolite trafficking and fuel sensitivity in human pluripotent stem cell-derived islets [ Cell Rep, 2023, 42(8):112970]	PubMed: 37556323
DELs enable the development of BRET probes for target engagement studies in cells [ Cell Chem Biol, 2023, 30(8):987-998.e24]	PubMed: 37490918
PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability [ EMBO Rep, 2023, e57234.]	PubMed: 37888778
Mitotic DNA damage promotes chromokinesin-mediated missegregation of polar chromosomes in cancer cells [ Mol Biol Cell, 2023, 34(5):ar47]	PubMed: 36989031
Nuclear chromosome locations dictate segregation error frequencies [ Nature, 2022, 607(7919):604-609]	PubMed: 35831506
Pancreas agenesis mutations disrupt a lead enhancer controlling a developmental enhancer cluster [ Dev Cell, 2022, 57(16):1922-1936.e9]	PubMed: 35998583

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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