1124329-14-1
中文名称
AZ3146
英文名称
9-Cyclopentyl-2-[[2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]-phenyl]amino]-7-methyl-7,9-dihydro-8H-purin-8-one
CAS
1124329-14-1
分子式
C24H32N6O3
分子量
453
MOL 文件
1124329-14-1.mol
更新日期
2023/03/20 15:41:23
1124329-14-1 结构式
基本信息
中文别名
MPS1抑制剂(AZ3146)9-环戊基-2-((2-甲氧基-4-((1-甲基哌啶-4-基)氧基)苯基)氨基)-7-甲基-7H-嘌呤-8(9H)-酮
9-环戊基-7,9-二氢-2-[[2-甲氧基-4-[(1-甲基-4-哌啶基)氧基]苯基]氨基]-7-甲基-8H-嘌呤-8-酮
9-环戊基-2-[[2-甲氧基-4-[(1-甲基哌啶-4-基)氧基]-苯基]氨基]-7-甲基-7,9-二氢-8H-嘌呤-8-酮
英文别名
CS-511AZ 3146
1124329-14-1
AZ 3146
AZ-3146
AZ3146 >=98% (HPLC)
AZ3146
AZ 3146
AZ-3146
AZ3146 Mps1 Inhibitor III AZ-3146
9-Cyclopentyl-2-({2-methoxy-4-[(1-methylpiperidin-4-yl)oxy]phenyl}amino)-7-methylpurin-8-one
9-Cyclopentyl-2-((2-methoxy-4-((1-methylpiperidin-4-yl)oxy)phenyl)amino)-7-methyl-7H-purin-8(9
9-cyclopentyl-2-(2-Methoxy-4-(1-Methylpiperidin-4-yloxy)phenylaMino)-7-Methyl-7H-purin-8(9H)-one
所属类别
生物化工：Kinesin 抑制剂物理化学性质
沸点621.0±65.0 °C(Predicted)
密度1.279
储存条件Store at +4°C
溶解度可溶于 DMSO（高达 10 mg/ml）或乙醇（高达至少 25 mg/ml）
酸度系数(pKa)8.29±0.10(Predicted)
形态固体
颜色米白色
稳定性DMSO或乙醇溶液可在-20℃下稳定储存1个月。
常见问题列表
生物活性
AZ 3146是一种选择性Mps1抑制剂，IC50为35 nM左右，有助于招募CENP-E(驱动蛋白相关的动力蛋白)，对FAK， JNK1， JNK2和Kit作用效果稍弱。体外研究
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.生物活性
AZ 3146是一种选择性Mps1抑制剂，IC50为35 nM左右，有助于聚集CENP-E(驱动蛋白相关的动力蛋白)，对FAK， JNK1， JNK2和Kit作用效果稍弱。靶点
| Target | Value |
|
Mps1
(Cell-free assay) | ~35 nM |
体外研究
AZ3146也抑制FAK，JNK1，JNK2 和 Kit。AZ3146显著抑制细胞中Mps1的磷酸化作用。Aurora B和BubR1的有丝分裂特异性磷酸形式不被AZ3146影响。AZ3146不抑制有丝分裂细胞中Cdk1 或aurora B。HeLa细胞用Nocodazole和2 μM AZ3146处理，仅短暂延迟有丝分裂，随后重新复制它们的基因组，表明AZ3146能够阻断SAC。AZ3146也会抑制已经建立的SAC信号，其不被nocodazole阻断，AZ3146也会显著加速有丝分裂结束。在其他未受到干扰的有丝分裂中，AZ3146使完成有丝分裂的时间从对照组的90分钟减少到32分钟。引人注目的是，~90% AZ3146处理的HeLa细胞发生异常有丝分裂，~50%进入分裂后期的细胞没有调整它们的染色体，~30%完成有丝分裂的细胞没有进行明显的染色体分离。AZ3146对Mad2的着丝粒定位具有显著作用，将其水平降低到~15%，但是它对Mad1的作用不明显，其水平保持在~60%。进入有丝分裂期前，Mps1被AZ3146抑制，随后Mad1和Mad2对着丝粒的聚集被阻止。然而，如果进入有丝分裂期后，Mps1被AZ3146抑制，Mad1–C-Mad2核心复合物仍然与着丝粒结合，但是O-Mad2不能完全聚集。