1124329-14-1
中文名稱
AZ3146
英文名稱
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 結(jié)構(gòu)式
基本信息
中文別名
MPS1抑制劑(AZ3146)9-環(huán)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-環(huán)戊基-7,9-二氫-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-環(huán)戊基-2-[[2-甲氧基-4-[(1-甲基哌啶-4-基)氧基]-苯基]氨基]-7-甲基-7,9-二氫-8H-嘌呤-8-酮
英文別名
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
所屬類別
生物化工：Kinesin 抑制劑物理化學(xué)性質(zhì)
沸點621.0±65.0 °C(Predicted)
密度1.279
儲存條件Store at +4°C
溶解度可溶于 DMSO（高達 10 mg/ml）或乙醇（高達至少 25 mg/ml）
酸度系數(shù)(pKa)8.29±0.10(Predicted)
形態(tài)固體
顏色米白色
穩(wěn)定性DMSO或乙醇溶液可在-20℃下穩(wěn)定儲存1個月。
常見問題列表
生物活性
AZ 3146是一種選擇性Mps1抑制劑，IC50為35 nM左右，有助于招募CENP-E(驅(qū)動蛋白相關(guān)的動力蛋白)，對FAK， JNK1， JNK2和Kit作用效果稍弱。體外研究
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是一種選擇性Mps1抑制劑，IC50為35 nM左右，有助于聚集CENP-E(驅(qū)動蛋白相關(guān)的動力蛋白)，對FAK， JNK1， JNK2和Kit作用效果稍弱。靶點
| Target | Value |
|
Mps1
(Cell-free assay) | ~35 nM |
體外研究
AZ3146也抑制FAK，JNK1，JNK2 和 Kit。AZ3146顯著抑制細胞中Mps1的磷酸化作用。Aurora B和BubR1的有絲分裂特異性磷酸形式不被AZ3146影響。AZ3146不抑制有絲分裂細胞中Cdk1 或aurora B。HeLa細胞用Nocodazole和2 μM AZ3146處理，僅短暫延遲有絲分裂，隨后重新復(fù)制它們的基因組，表明AZ3146能夠阻斷SAC。AZ3146也會抑制已經(jīng)建立的SAC信號，其不被nocodazole阻斷，AZ3146也會顯著加速有絲分裂結(jié)束。在其他未受到干擾的有絲分裂中，AZ3146使完成有絲分裂的時間從對照組的90分鐘減少到32分鐘。引人注目的是，~90% AZ3146處理的HeLa細胞發(fā)生異常有絲分裂，~50%進入分裂后期的細胞沒有調(diào)整它們的染色體，~30%完成有絲分裂的細胞沒有進行明顯的染色體分離。AZ3146對Mad2的著絲粒定位具有顯著作用，將其水平降低到~15%，但是它對Mad1的作用不明顯，其水平保持在~60%。進入有絲分裂期前，Mps1被AZ3146抑制，隨后Mad1和Mad2對著絲粒的聚集被阻止。然而，如果進入有絲分裂期后，Mps1被AZ3146抑制，Mad1–C-Mad2核心復(fù)合物仍然與著絲粒結(jié)合，但是O-Mad2不能完全聚集。