KU-55933
别名: ATM Kinase Inhibitor
KU-55933是一种有效的，特异性ATM抑制剂，在无细胞试验中IC50/Ki为12.9 nM/2.2 nM，与DNA-PK， PI3K/PI4K， ATR和mTOR相比，对ATM具有高度选择性。KU‑55933 (ATM Kinase Inhibitor)可抑制 autophagy‑initiating kinase ULK1 的激活从而导致自噬的显著减少。
KU-55933 Chemical Structure
CAS: 587871-26-9
产品质控
批次：
纯度：
99.95%
99.95
KU-55933相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| HepG2 | Growth Inhibition Assay | 10 μM | 24 h | blocks SC-III3-induced S phase arrest | 25527123 |
| HepG2 | Function Assay | 10 μM | 24 h | suppresses the phosphorylations of ATM on Ser1981, Chk1 on Ser345, Chk2 on Thr68, and Cdk2 on Tyr15 induced by SC-III3 | 25527123 |
| MCF10A | Growth Inhibition Assay | 10 μM | 24 h | potentiates the cytotoxicity of GA | 24150595 |
| HL-60 | Function Assay | 10 μM | 0.5 h | reduces phosphorylation of Chk2 | 23934411 |
| MCF-7 | Growth Inhibition Assay | 1-100μM | 24 h | inhibits the cell proliferation | 23185347 |
| HeLa | Growth Inhibition Assay | 1-100μM | 24 h | inhibits the cell proliferation | 23185347 |
| SH-SY5Y | Function Assay | 10 μM | 24 h | inhibits clioquinol-induced phosphorylation of p53 | 22627294 |
| IMR-32 | Function Assay | 10 μM | 24 h | inhibits clioquinol-induced phosphorylation of p53 | 22627294 |
| A549 | Function Assay | 10 μM | 1 h | suppresses Nano-Co-induced p53 accumulation | 22559321 |
| T47D | Function Assay | 20 mM | 24 h | prevents IR-induced degradation of IκBα | 21144805 |
| A29 MEF | Function Assay | 10 μM | 1h | blocks the phosphorylation of Akt at Ser473 | 20053781 |
| MDA-MB-453 | Growth Inhibition Assay | 5-40 μM | 72 h | IC50 of 10 μM | 20053781 |
| PC-3 | Growth Inhibition Assay | 5-40 μM | 72 h | IC50 of 10 μM | 20053781 |
| BJ | Function assay | 10 uM | 10 days | Suppression of senescence in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay | 16767085 |
| BJ | Function assay | 10 uM | 10 days | Inhibition of ataxia telangiectasia-mutated in human BJ cells assessed as increase in cell number at 10 uM after 10 days by senescence reversal assay | 16767085 |
| MCF7 | Function assay | 10 uM | 10 mins | Sensitization of infrared-induced DNA damage in human MCF7 cells assessed as reduction in colony formation at 10 uM pretreated for 10 mins followed by irradiation for 4 hrs measured after 10 days by crystal violet staining analysis | 26632965 |
| KATO III | Growth Inhibition Assay | 2.5/5/7.5 μM | enhances the toxicity of olaparib | 24841718 | |
| hTCEpi | Growth Inhibition Assay | 10 μM | prevents the cytopathic effect of HSV-1 | 24370835 | |
| MCF7 | Function assay | 1 hr | Inhibition of ATM kinase in human MCF7 cells after 1 hr by immunofluorescence assay, IC50 = 0.3 μM. | 26632965 | |
| KOSC-2 | Growth Inhibition Assay | IC50=26.9075 μM | SANGER | ||
| DEL | Growth Inhibition Assay | IC50=26.8356 μM | SANGER | ||
| GT3TKB | Growth Inhibition Assay | IC50=26.5342 μM | SANGER | ||
| MDA-MB-415 | Growth Inhibition Assay | IC50=26.5033 μM | SANGER | ||
| GI-1 | Growth Inhibition Assay | IC50=25.7055 μM | SANGER | ||
| BFTC-905 | Growth Inhibition Assay | IC50=25.5944 μM | SANGER | ||
| QIMR-WIL | Growth Inhibition Assay | IC50=25.1858 μM | SANGER | ||
| PANC-08-13 | Growth Inhibition Assay | IC50=25.0938 μM | SANGER | ||
| SK-MEL-30 | Growth Inhibition Assay | IC50=24.4662 μM | SANGER | ||
| CHL-1 | Growth Inhibition Assay | IC50=23.7292 μM | SANGER | ||
| Ramos-2G6-4C10 | Growth Inhibition Assay | IC50=22.96 μM | SANGER | ||
| SNU-449 | Growth Inhibition Assay | IC50=22.8748 μM | SANGER | ||
| HCC2157 | Growth Inhibition Assay | IC50=22.8054 μM | SANGER | ||
| LB1047-RCC | Growth Inhibition Assay | IC50=22.5879 μM | SANGER | ||
| YH-13 | Growth Inhibition Assay | IC50=22.5123 μM | SANGER | ||
| Mewo | Growth Inhibition Assay | IC50=22.5073 μM | SANGER | ||
| JVM-3 | Growth Inhibition Assay | IC50=22.506 μM | SANGER | ||
| HSC-3 | Growth Inhibition Assay | IC50=21.1835 μM | SANGER | ||
| U031 | Growth Inhibition Assay | IC50=21.1489 μM | SANGER | ||
| D-283MED | Growth Inhibition Assay | IC50=20.5339 μM | SANGER | ||
| A704 | Growth Inhibition Assay | IC50=19.8305 μM | SANGER | ||
| HCC70 | Growth Inhibition Assay | IC50=19.489 μM | SANGER | ||
| MLMA | Growth Inhibition Assay | IC50=19.0557 μM | SANGER | ||
| 697 | Growth Inhibition Assay | IC50=19.0201 μM | SANGER | ||
| HuP-T3 | Growth Inhibition Assay | IC50=18.5888 μM | SANGER | ||
| NCI-H2030 | Growth Inhibition Assay | IC50=18.1997 μM | SANGER | ||
| HCC2998 | Growth Inhibition Assay | IC50=17.6733 μM | SANGER | ||
| NCI-H82 | Growth Inhibition Assay | IC50=17.4573 μM | SANGER | ||
| CTB-1 | Growth Inhibition Assay | IC50=17.2259 μM | SANGER | ||
| NCI-SNU-1 | Growth Inhibition Assay | IC50=17.1269 μM | SANGER | ||
| SK-MEL-28 | Growth Inhibition Assay | IC50=17.0475 μM | SANGER | ||
| GCIY | Growth Inhibition Assay | IC50=16.7905 μM | SANGER | ||
| ChaGo-K-1 | Growth Inhibition Assay | IC50=16.6568 μM | SANGER | ||
| NCI-H1793 | Growth Inhibition Assay | IC50=16.4712 μM | SANGER | ||
| LXF-289 | Growth Inhibition Assay | IC50=16.2747 μM | SANGER | ||
| HuH-7 | Growth Inhibition Assay | IC50=16.2674 μM | SANGER | ||
| 8305C | Growth Inhibition Assay | IC50=16.1889 μM | SANGER | ||
| KG-1 | Growth Inhibition Assay | IC50=16.0996 μM | SANGER | ||
| VM-CUB-1 | Growth Inhibition Assay | IC50=15.9849 μM | SANGER | ||
| DBTRG-05MG | Growth Inhibition Assay | IC50=15.6111 μM | SANGER | ||
| D-423MG | Growth Inhibition Assay | IC50=15.5236 μM | SANGER | ||
| Hs-578-T | Growth Inhibition Assay | IC50=15.4182 μM | SANGER | ||
| DOK | Growth Inhibition Assay | IC50=15.3329 μM | SANGER | ||
| COLO-684 | Growth Inhibition Assay | IC50=14.1569 μM | SANGER | ||
| CAL-12T | Growth Inhibition Assay | IC50=13.617 μM | SANGER | ||
| KP-N-YS | Growth Inhibition Assay | IC50=12.6354 μM | SANGER | ||
| ES7 | Growth Inhibition Assay | IC50=11.788 μM | SANGER | ||
| LB2241-RCC | Growth Inhibition Assay | IC50=11.7186 μM | SANGER | ||
| GOTO | Growth Inhibition Assay | IC50=11.6996 μM | SANGER | ||
| J-RT3-T3-5 | Growth Inhibition Assay | IC50=11.2417 μM | SANGER | ||
| NCI-H1838 | Growth Inhibition Assay | IC50=11.1865 μM | SANGER | ||
| NCI-H1437 | Growth Inhibition Assay | IC50=9.8097 μM | SANGER | ||
| KM12 | Growth Inhibition Assay | IC50=9.21142 μM | SANGER | ||
| SK-MEL-3 | Growth Inhibition Assay | IC50=8.28575 μM | SANGER | ||
| HH | Growth Inhibition Assay | IC50=8.27671 μM | SANGER | ||
| LoVo | Growth Inhibition Assay | IC50=6.93239 μM | SANGER | ||
| CAL-72 | Growth Inhibition Assay | IC50=5.48084 μM | SANGER | ||
| LAMA-84 | Growth Inhibition Assay | IC50=4.58465 μM | SANGER | ||
| HuO-3N1 | Growth Inhibition Assay | IC50=4.17142 μM | SANGER | ||
| DU-145 | Growth Inhibition Assay | IC50=3.27352 μM | SANGER | ||
| RVH-421 | Growth Inhibition Assay | IC50=27.2921 μM | SANGER | ||
| EW-13 | Growth Inhibition Assay | IC50=27.4308 μM | SANGER | ||
| 639-V | Growth Inhibition Assay | IC50=27.5119 μM | SANGER | ||
| A2780 | Growth Inhibition Assay | IC50=27.641 μM | SANGER | ||
| SW982 | Growth Inhibition Assay | IC50=27.9052 μM | SANGER | ||
| SW1710 | Growth Inhibition Assay | IC50=28.0981 μM | SANGER | ||
| HCC1569 | Growth Inhibition Assay | IC50=28.4897 μM | SANGER | ||
| MV-4-11 | Growth Inhibition Assay | IC50=28.5735 μM | SANGER | ||
| BHT-101 | Growth Inhibition Assay | IC50=28.6572 μM | SANGER | ||
| Ca9-22 | Growth Inhibition Assay | IC50=28.714 μM | SANGER | ||
| HAL-01 | Growth Inhibition Assay | IC50=28.7615 μM | SANGER | ||
| D-263MG | Growth Inhibition Assay | IC50=29.344 μM | SANGER | ||
| NEC8 | Growth Inhibition Assay | IC50=29.5548 μM | SANGER | ||
| EKVX | Growth Inhibition Assay | IC50=31.5847 μM | SANGER | ||
| EM-2 | Growth Inhibition Assay | IC50=31.6304 μM | SANGER | ||
| MFM-223 | Growth Inhibition Assay | IC50=31.8098 μM | SANGER | ||
| SK-PN-DW | Growth Inhibition Assay | IC50=32.1406 μM | SANGER | ||
| HuO9 | Growth Inhibition Assay | IC50=32.5282 μM | SANGER | ||
| MHH-PREB-1 | Growth Inhibition Assay | IC50=32.6234 μM | SANGER | ||
| OVCAR-4 | Growth Inhibition Assay | IC50=32.8363 μM | SANGER | ||
| NCI-H1648 | Growth Inhibition Assay | IC50=32.8651 μM | SANGER | ||
| MKN1 | Growth Inhibition Assay | IC50=34.1101 μM | SANGER | ||
| KYSE-450 | Growth Inhibition Assay | IC50=34.6444 μM | SANGER | ||
| ES8 | Growth Inhibition Assay | IC50=34.8975 μM | SANGER | ||
| MS-1 | Growth Inhibition Assay | IC50=34.9554 μM | SANGER | ||
| HOP-92 | Growth Inhibition Assay | IC50=35.9277 μM | SANGER | ||
| SKG-IIIa | Growth Inhibition Assay | IC50=36.2561 μM | SANGER | ||
| TE-11 | Growth Inhibition Assay | IC50=36.5243 μM | SANGER | ||
| SK-NEP-1 | Growth Inhibition Assay | IC50=37.6744 μM | SANGER | ||
| DB | Growth Inhibition Assay | IC50=37.9185 μM | SANGER | ||
| IA-LM | Growth Inhibition Assay | IC50=38.0239 μM | SANGER | ||
| COLO-829 | Growth Inhibition Assay | IC50=38.4159 μM | SANGER | ||
| TGBC11TKB | Growth Inhibition Assay | IC50=39.1408 μM | SANGER | ||
| CAL-51 | Growth Inhibition Assay | IC50=40.0612 μM | SANGER | ||
| NCI-H2228 | Growth Inhibition Assay | IC50=40.3662 μM | SANGER | ||
| C32 | Growth Inhibition Assay | IC50=40.4024 μM | SANGER | ||
| KU-19-19 | Growth Inhibition Assay | IC50=40.7683 μM | SANGER | ||
| KNS-62 | Growth Inhibition Assay | IC50=40.8381 μM | SANGER | ||
| FADU | Growth Inhibition Assay | IC50=41.2502 μM | SANGER | ||
| CAL-33 | Growth Inhibition Assay | IC50=42.6749 μM | SANGER | ||
| CHP-134 | Growth Inhibition Assay | IC50=42.8496 μM | SANGER | ||
| HDLM-2 | Growth Inhibition Assay | IC50=42.9084 μM | SANGER | ||
| NBsusSR | Growth Inhibition Assay | IC50=43.0725 μM | SANGER | ||
| SW954 | Growth Inhibition Assay | IC50=43.1053 μM | SANGER | ||
| HCC1806 | Growth Inhibition Assay | IC50=43.411 μM | SANGER | ||
| VMRC-RCZ | Growth Inhibition Assay | IC50=43.4586 μM | SANGER | ||
| A549 | Growth Inhibition Assay | IC50=43.931 μM | SANGER | ||
| NKM-1 | Growth Inhibition Assay | IC50=43.9558 μM | SANGER | ||
| DMS-273 | Growth Inhibition Assay | IC50=44.7567 μM | SANGER | ||
| TYK-nu | Growth Inhibition Assay | IC50=45.1234 μM | SANGER | ||
| KALS-1 | Growth Inhibition Assay | IC50=45.146 μM | SANGER | ||
| A101D | Growth Inhibition Assay | IC50=45.4456 μM | SANGER | ||
| G-361 | Growth Inhibition Assay | IC50=46.2138 μM | SANGER | ||
| KARPAS-299 | Growth Inhibition Assay | IC50=46.3516 μM | SANGER | ||
| RS4-11 | Growth Inhibition Assay | IC50=46.542 μM | SANGER | ||
| HT-1376 | Growth Inhibition Assay | IC50=46.7426 μM | SANGER | ||
| SK-N-AS | Growth Inhibition Assay | IC50=46.7822 μM | SANGER | ||
| MG-63 | Growth Inhibition Assay | IC50=46.9036 μM | SANGER | ||
| EPLC-272H | Growth Inhibition Assay | IC50=46.9503 μM | SANGER | ||
| BALL-1 | Growth Inhibition Assay | IC50=47.832 μM | SANGER | ||
| LCLC-97TM1 | Growth Inhibition Assay | IC50=48.202 μM | SANGER | ||
| HO-1-N-1 | Growth Inhibition Assay | IC50=48.9676 μM | SANGER | ||
| MFE-280 | Growth Inhibition Assay | IC50=49.4617 μM | SANGER | ||
| NCI-H526 | Growth Inhibition Assay | IC50=49.8163 μM | SANGER | ||
| D-566MG | Growth Inhibition Assay | IC50=49.9096 μM | SANGER | ||
| BB30-HNC | Growth Inhibition Assay | IC50=49.9498 μM | SANGER | ||
| SK-N-DZ | Growth Inhibition Assay | IC50=50.0481 μM | SANGER | ||
| U2OS | Function assay | Inhibition of ATM in human U2OS cells assessed as inhibition of p53 phosphorylation at Ser15 residue, IC50 = 0.25 μM. | 26632965 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | KU-55933是一种有效的，特异性ATM抑制剂，在无细胞试验中IC50/Ki为12.9 nM/2.2 nM，与DNA-PK， PI3K/PI4K， ATR和mTOR相比，对ATM具有高度选择性。KU‑55933 (ATM Kinase Inhibitor)可抑制 autophagy‑initiating kinase ULK1 的激活从而导致自噬的显著减少。 | ||
|---|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | KU-55933是有效的特定ATM抑制剂，IC50为13 nM，Ki值为2.2 nM。KU-55933也抑制DNA-PK和PI3K，IC50分别为2.5和16.6 μM。KU-55933也抑制mTOR活性，IC50为9.3 μM。KU-55933有效作用于ATM依赖的磷酸化作用。KU-55933抑制ATM依赖的磷酸化作用，存在剂量依赖性，IC50为300 nM。小于30 μM时，KU-58050不能抑制p53的ATM-依赖性磷酸化作用（位点为第15位丝氨酸）。在UV-诱导的H2AX（位点为第139位丝氨酸）, NBS1（位点为第343为丝氨酸）, CHK1（位点为第345位丝氨酸）,及SMC1（位点为第966位丝氨酸）中，加入KU-55933没有明显作用效果。紫外处理时，KU-55933切除由电离辐射诱导的ATM磷酸化底物。KU-55933使HeLa细胞对电离辐射敏感。在癌细胞中，KU-55933抑制生长因子诱导的Akt的磷酸化作用。KU-55933抑制癌细胞增殖。KU-55933抑制ATM，通过阻断下游TAp63α的激活，提高存活力。[2] | |||
|---|---|---|---|---|
| 激酶实验 | 纯化的酶实验 | |||
| 通过免疫沉淀反应从HeLa核蛋白萃取中获得用于体外研究的ATM，在反应buffer中，把兔多克隆抗血清加到ATM羧基端第400个氨基酸处，buffer包含25 mM HEPES (pH为7.4), 2 mM MgCl2, 250 mM KCl, 500 μM EDTA, 100 μM Na3VO4, 10% v/v 甘油, 及0.1% v/v Igepal。和蛋白A凝胶温育1小时，然后进行离心作用，从核蛋白中分离ATM抗体复合物。在96孔板中，包含ATM的凝胶珠和1 μg 底物GST-p53N66 (p53的氮端第66位氨基酸与GST融合)在ATM实验buffer中37oC下温育，buffer包括25 mM HEPES (pH 为7.4), 75 mM NaCl, 3 mM MgCl2, 2 mM MnCl2, 50 μM Na3VO4, 500 μM DTT, 及5% v/v甘油。震荡10分钟后，加入ATP，最终浓度为50 μM，在37oC反应持续1小时。按250×g转速4oC下离心10分钟，除去ATM凝胶珠，上清液转移到96孔板上，在室温下温育1.5小时。然后用PBS冲洗，烘干，加入p-p53(Ser15)抗体用于ELISA分析。使用增强的化学发光溶液产生信号和化学发光。 | ||||
| 细胞实验 | 细胞系 | U2OS细胞 | ||
| 浓度 | 10 μM | |||
| 孵育时间 | 2小时 | |||
| 方法 | U2OS细胞经过电离辐射(3, 5, 或15 Gy) 或者UV处理(5或50 J/m2)，通过p-p53（Ser15）和p53 的Western blot分析而测定ATM反应。在不同时间点获得细胞萃取物，SDS-PAGE分离蛋白，加入p-p53(Ser15)抗体，ATM增多。加入p53抗体观察到p53随着时间变化趋于稳定。为了测定KU-55933的IC50值，使用p-p53(Ser15)抗体检测KU-55933抑制ATM的效果。KU-55933加到细胞中，预温育1小时，然后进行电离辐射。在体外，使用扫描密度测定法测定IC50值。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-AKT(Ser473) / p-AKT(Thr308) PARP / Cleaved PARP / Caspase-3 / Cleaved caspase-3 ATM-S1981 / ATM / p-p53(S15) / p53 p21 / p27 / p53 |
|
22739265 | |
| Immunofluorescence | p-S824 KAP1 / ZEBRA |
|
28249048 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | KU-55933抑制ATM依赖的STAT3激活，通过上调DR5表达增强TRAIL调节的凋亡,抑制STAT3 和NF-κB都和下调cFLIP有关，伴随着凋亡水平上升。ATM抑制剂KU-55933 影响TRAIL调节的凋亡的效果比JAK2抑制剂AG490或STAT3β过量表达都高。[3] | |
|---|---|---|
| 动物实验 | Animal Models | 携带LU1205细胞的BALB/c nu/nu鼠 |
| Dosages | 10 μM | |
| Administration | -- | |
化学信息&溶解度
| 分子量 | 395.49 | 分子式 | C21H17NO3S2 |
| CAS号 | 587871-26-9 | SDF | Download KU-55933 SDF |
| Smiles | C1COCCN1C2=CC(=O)C=C(O2)C3=C4C(=CC=C3)SC5=CC=CC=C5S4 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 39 mg/mL ( (98.61 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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