KU 55933
(Synonyms: 2-吗啉-4-基-6-噻蒽-1-基吡喃-4-酮) 目录号 : GC11118
KU 55933是一种高效且特异的ATM激酶抑制剂，能够使人类肿瘤细胞对电离辐射和化疗药物更加敏感。KU 55933在体外的IC₅₀值为13nM，Ki值为2.2nM。
Cas No.:587871-26-9
Sample solution is provided at 25 µL, 10mM.
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KU 55933 is a potent and specific ATM kinase inhibitor that sensitizes human tumor cells to ionizing radiation and chemotherapeutic agents[1]. KU 55933 has an IC50 of 13nM and Ki of 2.2nM in vitro[2].
In vitro, The ATM inhibitor KU 55933 (10μM; 1h) suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt[3]. Inhibition of ATM with KU 55933 (10μM; 24h or 72h) sensitizes endometrial cancer cell lines to Olaparib[4]. KU 55933 (0.01-20μM; 24h) is neuroprotective against the doxorubicin-induced cell damage in UN- and RA-SH-SY5Y cells[5].
In vivo, Administration of KU 55933 (8mg/kg; 12 weeks; i.v.) to apolipoprotein E-deficient mice inhibited Smad1/5 activation in endothelial cells (ECs) in atherosclerosis-susceptible regions, thereby suppressing endothelial cell proliferation and inflammation and attenuating atherosclerotic lesions in these mice[3]. KU 55933 (1mg/kg; 4 weeks; i.p.) treatment inhibits tumor growth and metastasis in mouse mammary tumors in vivo through the inhibition of GLUT1 translocation and vimentin expression[6].
References:
[1] Wei SY, Fu WS, Liu CH, et al. Identification of KU-55933 as an anti-atherosclerosis compound by using a hemodynamic-based high-throughput drug screening platform. Proc Natl Acad Sci U S A. 2024 Jan 30;121(5):e2318718121.
[2] Golding SE, Rosenberg E, Valerie N, et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther. 2009 Oct;8(10):2894-902.
[3] Zhang A, Zhang L, Xie X, et al. Inhibition of ATM with KU-55933 Sensitizes Endometrial Cancer Cell Lines to Olaparib. Onco Targets Ther. 2023 Dec 19;16:1061-1071.
[4] Chwastek J, Jantas D, Lasoń W. The ATM kinase inhibitor KU-55933 provides neuroprotection against hydrogen peroxide-induced cell damage via a γH2AX/p-p53/caspase-3-independent mechanism: Inhibition of calpain and cathepsin D. Int J Biochem Cell Biol. 2017 Jun;87:38-53.
[5] Li Y, Yang DQ. The ATM inhibitor KU-55933 suppresses cell proliferation and induces apoptosis by blocking Akt in cancer cells with overactivated Akt. Mol Cancer Ther. 2010 Jan;9(1):113-25.
[6] Harris BRE, Zhang Y, Tao J, et al. ATM inhibitor KU-55933 induces apoptosis and inhibits motility by blocking GLUT1-mediated glucose uptake in aggressive cancer cells with sustained activation of Akt. FASEB J. 2021 Apr;35(4):e21264.
KU 55933是一种高效且特异的ATM激酶抑制剂，能够使人类肿瘤细胞对电离辐射和化疗药物更加敏感[1]。KU 55933在体外的IC₅₀值为13nM，Ki值为2.2nM[2]。
在体外实验中，ATM抑制剂KU 55933（10μM; 1小时）通过阻断过度激活的Akt，抑制癌细胞的增殖并诱导凋亡[3]。通过KU 55933（10μM; 24小时或72小时）抑制ATM，可使子宫内膜癌细胞系对奥拉帕尼更加敏感[4]。KU 55933（0.01-20μM; 24小时）对阿霉素诱导的UN-和RA-SH-SY5Y细胞损伤具有神经保护作用[5]。
在体内实验中，对缺乏载脂蛋白E的小鼠给予KU 55933（8mg/kg; 12周; 静脉注射），抑制了易患动脉粥样硬化区域的内皮细胞（ECs）中Smad1/5的激活，从而抑制了内皮细胞的增殖和炎症，并减轻了这些小鼠的动脉粥样硬化病变[3]。KU 55933治疗通过抑制GLUT1的转位和波形蛋白的表达，在体内抑制小鼠乳腺肿瘤的生长和转移[6]。
| Cell experiment [1]: | |
Cell lines | Ishikawa and Hec-108 cells |
Preparation Method | Ishikawa and Hec-108 cells were cultured to 30-50% confluence and then treated with Olaparib (50µM) alone or in combination with KU 55933 (10µM) for 24h. The cells were then harvested, washed with cold PBS and stained with PI and FITC-Annexin V. Apoptosis was detected by CytoFLEX and analyzed by CytExpert software. |
Reaction Conditions | 10μM; 24h |
Applications | Inhibition of ATM with KU 55933 sensitizes endometrial cancer cell lines to Olaparib. |
| Animal experiment [2]: | |
Animal models | Six-week-old male ApoE−/− mice |
Preparation Method | ApoE−/− mice fed a high-fat diet (HFD) were tail-vein injected with KU 55933 (8mg/kg) or vehicle (DMSO in saline) for 12 weeks. After the experiment, biochemical analysis was performed on the mouse plasma, and the mouse aorta and aortic roots were stained with Oil Red O and H&E. |
Dosage form | 8mg/kg; 12 weeks; i.v. |
Applications | Administration of KU 55933 to apolipoprotein E-deficient mice inhibited Smad1/5 activation in endothelial cells (ECs) in atherosclerosis-susceptible regions, thereby suppressing endothelial cell proliferation and inflammation and attenuating atherosclerotic lesions in these mice. |
References: | |
| Cas No. | 587871-26-9 | SDF | |
| 别名 | 2-吗啉-4-基-6-噻蒽-1-基吡喃-4-酮 | ||
| 化学名 | 2-morpholin-4-yl-6-thianthren-1-ylpyran-4-one | ||
| Canonical SMILES | C1COCCN1C2=CC(=O)C=C(O2)C3=C4C(=CC=C3)SC5=CC=CC=C5S4 | ||
| 分子式 | C21H17NO3S2 | 分子量 | 395.49 |
| 溶解度 | ≥ 41.7mg/mL in DMSO with gentle warming | 储存条件 | Desiccate at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5285 mL | 12.6425 mL | 25.2851 mL |
| 5 mM | 0.5057 mL | 2.5285 mL | 5.057 mL |
| 10 mM | 0.2529 mL | 1.2643 mL | 2.5285 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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