AT9283
AT9283是一种有效的JAK2/3抑制剂，无细胞试验中IC50为1.2 nM/1.1 nM；对Aurora A/B，Abl1(T315I)也有效。
AT9283 Chemical Structure
CAS: 896466-04-9
产品质控
批次：
纯度：
99.82%
99.82
AT9283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 |
|---|---|---|---|---|---|
| Sf9 | Function assay | 10 uM | 60 mins | Displacement of BODIPY-ATP from C-terminal thrombin-cleavable hexa-histidine tagged human JAK2 JH2 pseudokinase domain (536 to 812 residues) W659A/W777A/F794H mutant expressed in baculovirus-infected Sf9 cells at 10 uM after 60 mins by high-throughput flu | 28626521 |
| HCT116 | Function assay | 20 mg/kg | Cmax in BALB/c mouse bearing human HCT116 cells at 20 mg/kg, ip, Cmax=8.4μM | 19143567 | |
| HCT116 | Function assay | 5 mg/kg | Cmax in BALB/c mouse bearing human HCT116 cells at 5 mg/kg, iv, Cmax=4.9μM | 19143567 | |
| HCT116 | Function assay | 10 mg/kg | Cmax in BALB/c mouse bearing human HCT116 cells at 10 mg/kg, po, Cmax=0.45μM | 19143567 | |
| HCT116 | Cytotoxicity assay | 10 to 14 days | Cytotoxicity against human HCT116 cells assessed as number of colonies after 10 to 14 days by colony forming assay, IC50=0.012μM | 19143567 | |
| HT-29 | Antitumor assay | 72 hrs | Antitumor activity against human HT-29 cells after 72 hrs by MTT assay, IC50=0.383μM | 23664099 | |
| A549 | Antitumor assay | 72 hrs | Antitumor activity against human A549 cells after 72 hrs by MTT assay, IC50=0.512μM | 23664099 | |
| LoVo | Antitumor assay | 72 hrs | Antitumor activity against human LoVo cells after 72 hrs by MTT assay, IC50=0.553μM | 23664099 | |
| K562 | Antitumor assay | 72 hrs | Antitumor activity against human K562 cells after 72 hrs by MTT assay, IC50=1.6μM | 23664099 | |
| U937 | Antitumor assay | 72 hrs | Antitumor activity against human U937 cells after 72 hrs by MTT assay, IC50=6.7μM | 23664099 | |
| BL21 (DE3) | Function assay | 30 mins | Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, IC50=0.685μM | 28351607 | |
| Sf9 | Function assay | Binding affinity to N-terminal TEV-cleavable hexa-histidine tagged human JAK2 JH1 domain (840 to 1132 residues) expressed in baculovirus-infected Sf9 cells by ITC assay, Kd=0.011μM | 28626521 | ||
| Sf9 | Function assay | Binding affinity to C-terminal thrombin-cleavable hexa-histidine tagged human JAK2 JH2 pseudokinase domain (536 to 812 residues) W659A/W777A/F794H mutant expressed in baculovirus-infected Sf9 cells by ITC assay, Kd=1.323μM | 28626521 | ||
| HCT116 | Function assay | Inhibition of Aurora B kinase in human HCT116 cells assessed as reduction in polyploid phenotype, IC50=0.03μM | 28918096 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| 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 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 29435139 | ||
| fibroblast cells | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory 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 | AT9283是一种有效的JAK2/3抑制剂，无细胞试验中IC50为1.2 nM/1.1 nM；对Aurora A/B，Abl1(T315I)也有效。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | AT9283是有效的pan-aurora 抑制剂。 | |||||||||||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | 在体外, AT9283有效抑制多种激酶，包括 Aurora A, Aurora B, JAK3, JAK2和 Abl，IC50分别为3 nM, 3 nM, 1.1 nM, 1.2 nM 和 4 nM。AT9283 作用于HCT116 细胞，通过抑制Aurora B 激酶活性，产生明显的多倍体表现型，IC50为30 nM。而且, AT9283也有效抑制HCT116形成集落。[1] |
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|---|---|---|---|---|
| 激酶实验 | Aurora A和 Aurora B激酶实验 | |||
| 在DELFIA格式中进行Aurora A 和 B实验。Aurora A 酶和AT9283 及 3 μM 肽底物 (生物素-CGPKGPGRRGRRRTSSFAEG)在 10 mM MOPS, pH 7, 0.1 mg/mL BSA, 0.001% Brij-35, 0.5% 甘油, 0.2 mM EDTA, 10 mM MgCl2, 0.01% β-巯基乙醇, 15 μM ATP,和2.5% DMSO混合物中温育。Aurora B 酶和AT9283,及3 μM 以上底物在25 mM Tris, pH 8.5, 5 mM MgCl2, 0.1 mg/mL BSA, 0.025% Tween-20, 1 mM DTT, 15 μM ATP, 和 2.5% DMSO的混合物中温育。Aurora A 和 Aurora B反应分别进行60分钟和45-90分钟,然后使用 EDTA进行淬火。反应混合物转移到亲和素包被的实验板上，通过时间分辨荧光技术(激发波长, 337 nm;发射波长, 620 nm)，使用特定磷酸抗体和铕标记的二抗测量磷酸化的肽。 | ||||
| 细胞实验 | 细胞系 | HCT 116 细胞 | ||
| 浓度 | 1 nM 到10 μM | |||
| 孵育时间 | 72 小时 | |||
| 方法 | HCT 116细胞培养在DMEM +10% FBS + GLUTAMAX I 中。细胞接种在黑色96孔平底组织培养板中，孔中含200 μL 培养基，在37oC 下温育约16小时，在湿润且含5% CO2 的环境下温育约16小时。使用9种不同浓度AT9283 (为 1 nM到 10 μM, 对照组为DMSO) 处理细胞，然后再温育72小时。 标记对细胞多倍体形态学的观察。记录产生明显多倍体所需AT9283的浓度。细胞按75−100个细胞/mL接种在有关培养基中，然后转移到6-或24-孔组织培养板上，然后覆盖培养16小时。AT9283(11 种浓度，0.1 nM 到 10 μM) 或对照组(DMSO) 加到复制孔中，DMSO终浓度为0.1%。随后加入AT9283，集落生长10和14天，计算最佳离散菌落数。集落在2 mL Carnoys 固定液(25% 乙酸,75% MeOH)中固定，然后在2 mL 0.4% w/v 结晶紫中染色。计算每孔中集落数。使用Prism Graphpad 软件绘制IC50曲线，通过S形剂量反应曲线计算IC50值。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Growth inhibition assay | Cell viability |
|
21430070 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | AT9283 按15 mg/kg和 20 mg/kg剂量作用于携带HCT116人结肠癌移植瘤的小鼠，持续16天，显著抑制肿瘤生长，抑制分别达67%和76%。此外, 与血浆(半衰期为0.5小时)相比，AT9283口服给药小鼠，也具有显著较长的半衰期。[1] |
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|---|---|---|
| 动物实验 | Animal Models | 后腿侧皮下注射HCT116细胞的雄性BALB/c小鼠 |
| Dosages | 15 mg/kg 和 20 mg/kg | |
| Administration | 腹腔注射 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT01145989 | Completed | Multiple Myeloma |
NCIC Clinical Trials Group|Astex Pharmaceuticals Inc.|Canadian Cancer Trials Group |
February 15 2011 | Phase 2 |
| NCT00443976 | Completed | Non-Hodgkins Lymphoma|Unspecified Adult Solid Tumor Protocol Specific |
NCIC Clinical Trials Group|Astex Pharmaceuticals Inc.|Canadian Cancer Trials Group |
January 30 2007 | Phase 1 |
化学信息&溶解度
| 分子量 | 381.43 | 分子式 | C19H23N7O2 |
| CAS号 | 896466-04-9 | SDF | Download AT9283 SDF |
| Smiles | C1CC1NC(=O)NC2=C(NN=C2)C3=NC4=C(N3)C=C(C=C4)CN5CCOCC5 | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 76 mg/mL ( (199.25 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 25 mg/mL (65.54 mM) Water : 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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