9-cyclopentyl-2-({2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]phenyl}amino)-7-methyl-8,9-dihydro-7H-purin-8-one

• ChemBase编号: 73196
• 分子式: C24H32N6O3
• 平均质量: 452.54928
• 单一同位素质量: 452.25358891
• SMILES: c1(cc(c(cc1)Nc1nc2c(cn1)n(c(=O)n2C1CCCC1)C)OC)OC1CCN(CC1)C
• Canonical SMILES: COc1cc(ccc1Nc1ncc2c(n1)n(C1CCCC1)c(=O)n2C)OC1CCN(CC1)C
• InChI: InChI=1S/C24H32N6O3/c1-28-12-10-17(11-13-28)33-18-8-9-19(21(14-18)32-3)26-23-25-15-20-22(27-23)30(24(31)29(20)2)16-6-4-5-7-16/h8-9,14-17H,4-7,10-13H2,1-3H3,(H,25,26,27)
• InChIKey: YUKWVHPTFRQHMF-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 9-cyclopentyl-2-({2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]phenyl}amino)-7-methyl-8,9-dihydro-7H-purin-8-one
• IUPAC传统名: 9-cyclopentyl-2-({2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]phenyl}amino)-7-methylpurin-8-one
• 别名: AZ 3146

登记号

• CAS号: 1124329-14-1
• PubChem SID: 162038116
• PubChem CID: 56973724

理论计算性质

• Acid pKa: 12.24688
• 质子受体: 7
• 质子供体: 1
• LogD (pH = 5.5): 0.13975327
• LogD (pH = 7.4): 1.8716863
• Log P: 3.0912325
• 摩尔折射率: 126.4273 cm^3
• 极化性: 48.085915 Å^3
• 极化表面积: 83.06 Å^2
• 可自由旋转的化学键: 6
• 里宾斯基五规则: true

分子性质

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Ksp

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S2731

Research Area

• Description: Cancer

Biological Activity

• Description: AZ3146 is a selective Mps1 inhibitor with IC50 of ~35 nM.
• Targets: Mps1
• IC50: ~35 nM ^[1]
• 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]

Protocol

• Protocol: Kinase Assay ^[1]
• In vitro kinase assays: 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.

References

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

参考文献

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