AZ 3146

製品コードS2731 バッチS273102

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	C₂₄H₃₂N₆O₃
	分子量	452.55	CAS No.	1124329-14-1
Solubility (25°C)*	体外	Ethanol	91 mg/mL (201.08 mM)
		DMSO	28 mg/mL (61.87 mM)
		Water	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	AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.
in vitro	AZ3146 also inhibits FAK, JNK1, JNK2 and Kit. AZ3146 significantly inhibits phosphorylation of Mps1 in cells. Mitotic-specific phospho forms of aurora B and BubR1 are not affected by AZ3146. AZ3146 does not inhibit Cdk1 or aurora B in mitotic cells. HeLa cells treated with nocodazole and 2 μM AZ3146 only delay mitosis briefly and then rereplicate their genomes, indicating that AZ3146 overrides the SAC. AZ3146 also inhibits an already established SAC signal, as after release from a nocodazole block, AZ3146 dramatically accelerates mitotic exit.During an otherwise unperturbed mitosis, AZ3146 reduces the time to complete mitosis from 90 minutes in controls to 32 minutes. Strikingly, ~90% of AZ3146-treated HeLa cells undergo abnormal mitoses, although ~50% enter anaphase without aligning all of their chromosomes, and ~30% exit mitosis without undergoing obvious chromosome segregation. AZ3146 has a dramatic effect on kinetochore localization of Mad2, reducing its levels to ~15%, but its effect on Mad1 is less pronounced, with levels remaining at ~60%. When Mps1 is inhibited by AZ3146 before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited by AZ3146 after mitotic entry, the Mad1–C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. ^[1]

製品説明

AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM, contributes to recruitment of CENP-E (kinesin-related motor protein), less potent to FAK, JNK1, JNK2, and Kit.

in vitro

AZ3146 also inhibits FAK, JNK1, JNK2 and Kit. AZ3146 significantly inhibits phosphorylation of Mps1 in cells. Mitotic-specific phospho forms of aurora B and BubR1 are not affected by AZ3146. AZ3146 does not inhibit Cdk1 or aurora B in mitotic cells. HeLa cells treated with nocodazole and 2 μM AZ3146 only delay mitosis briefly and then rereplicate their genomes, indicating that AZ3146 overrides the SAC. AZ3146 also inhibits an already established SAC signal, as after release from a nocodazole block, AZ3146 dramatically accelerates mitotic exit.During an otherwise unperturbed mitosis, AZ3146 reduces the time to complete mitosis from 90 minutes in controls to 32 minutes. Strikingly, ~90% of AZ3146-treated HeLa cells undergo abnormal mitoses, although ~50% enter anaphase without aligning all of their chromosomes, and ~30% exit mitosis without undergoing obvious chromosome segregation. AZ3146 has a dramatic effect on kinetochore localization of Mad2, reducing its levels to ~15%, but its effect on Mad1 is less pronounced, with levels remaining at ~60%. When Mps1 is inhibited by AZ3146 before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited by AZ3146 after mitotic entry, the Mad1–C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. ^[1]

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	For kinase assays, 500 ng His-tagged human Mps1Cat encoding amino acids 510-857 is added to buffer (25 mM Tris-HCl, pH 7.4, 100 mM NaCl, 50 μg/mL BSA, 0.1 mM EGTA, 0.1% β-mercaptoethanol, 10 mM MgCl₂, and 0.5 μg/mL myelin basic protein), AZ3146, and 100 μM γ-[³²P]ATP (2 μCi/assay). Reactions are incubated at 30°C for 20 minutes, spotted onto P81 paper, washed in 0.5% phosphoric acid, and immersed in acetone. Phosphate incorporation is determined by scintillation counting.

参考

[1] Hewitt L, et al. J Cell Biol, 2010, 190(1), 25-34.

カスタマーフィードバック

: Data from [Oncogenesis, 2014, 21, 3:e100]

: Data from [Data independently produced by J Biol Chem, 2013, 288(49), 35149-58]

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：

Design and Validation of Flim-timer for Measuring Protein Turnover in Cells Using Fluorescence Lifetime [ Research Square, 2024, 10.21203/rs.3.rs-2161438/v1]	PubMed: none
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505]	PubMed: 37845213
Selective utilization of non-homologous end-joining and homologous recombination for DNA repair during meiotic maturation in mouse oocytes [ Cell Prolif, 2023, 56(4):e13384]	PubMed: 36564861
CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer [ Int J Mol Sci, 2023, 24(20)15262]	PubMed: 37894942
CWH43 Is a Novel Tumor Suppressor Gene with Negative Regulation of TTK in Colorectal Cancer [ Int J Mol Sci, 2023, 24(20)15262]	PubMed: 37894942
Remarkable Synergy When Combining EZH2 Inhibitors with YM155 Is H3K27me3-Independent [ Cancers (Basel), 2022, 15(1)208]	PubMed: 36612203
Mitotic phosphorylation of tumor suppressor DAB2IP maintains spindle assembly checkpoint and chromosomal stability through activating PLK1-Mps1 signal pathway and stabilizing mitotic checkpoint complex [ Oncogene, 2021, 10.1038/s41388-021-02106-8]	PubMed: 34775484
Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation [ Nat Cell Biol, 2020, 22(7):856-867]	PubMed: 32601372
A kinase-independent function for AURORA-A in replisome assembly during DNA replication initiation [ Nucleic Acids Res, 2020, gkaa570]	PubMed: 32652013
Single-Chromosomal Gains Can Function as Metastasis Suppressors and Promoters in Colon Cancer. [ Dev Cell, 2020, 52(4):413-428]	PubMed: 32097652

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。