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AT9283
AT9283是一種有效的JAK2/3抑制劑，無細胞試驗中IC50為1.2 nM/1.1 nM；對Aurora A/B，Abl1(T315I)也有效。
AT9283 Chemical Structure
CAS: 896466-04-9
產品質控
批次：
純度：
99.82%
99.82
AT9283相關產品
相關信號通路圖
細胞實驗數據示例
| 細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
|---|---|---|---|---|---|
| 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 | ||
| 點擊查看更多細胞系數據 | |||||
生物活性
| 產品描述 | AT9283是一種有效的JAK2/3抑制劑，無細胞試驗中IC50為1.2 nM/1.1 nM；對Aurora A/B，Abl1(T315I)也有效。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | AT9283是有效的pan-aurora 抑制劑。 | |||||||||||
| 靶點 |
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| 體外研究(In Vitro) | ||||
| 體外研究活性 | 在體外, AT9283有效抑制多種激酶，包括 Aurora A, Aurora B, JAK3, JAK2和 Abl，IC50分別為3 nM, 3 nM, 1.1 nM, 1.2 nM 和 4 nM。AT9283 作用于HCT116 細胞，通過抑制Aurora B 激酶活性，產生明顯的多倍體表現(xiàn)型，IC50為30 nM。而且, AT9283也有效抑制HCT116形成集落。[1] |
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|---|---|---|---|---|
| 激酶實驗 | Aurora A和 Aurora B激酶實驗 | |||
| 在DELFIA格式中進行Aurora A 和 B實驗。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-巰基乙醇, 15 μM ATP,和2.5% DMSO混合物中溫育。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的混合物中溫育。Aurora A 和 Aurora B反應分別進行60分鐘和45-90分鐘,然后使用 EDTA進行淬火。反應混合物轉移到親和素包被的實驗板上，通過時間分辨熒光技術(激發(fā)波長, 337 nm;發(fā)射波長, 620 nm)，使用特定磷酸抗體和銪標記的二抗測量磷酸化的肽。 | ||||
| 細胞實驗 | 細胞系 | HCT 116 細胞 | ||
| 濃度 | 1 nM 到10 μM | |||
| 孵育時間 | 72 小時 | |||
| 方法 | HCT 116細胞培養(yǎng)在DMEM +10% FBS + GLUTAMAX I 中。細胞接種在黑色96孔平底組織培養(yǎng)板中，孔中含200 μL 培養(yǎng)基，在37oC 下溫育約16小時，在濕潤且含5% CO2 的環(huán)境下溫育約16小時。使用9種不同濃度AT9283 (為 1 nM到 10 μM, 對照組為DMSO) 處理細胞，然后再溫育72小時。 標記對細胞多倍體形態(tài)學的觀察。記錄產生明顯多倍體所需AT9283的濃度。細胞按75−100個細胞/mL接種在有關培養(yǎng)基中，然后轉移到6-或24-孔組織培養(yǎng)板上，然后覆蓋培養(yǎng)16小時。AT9283(11 種濃度，0.1 nM 到 10 μM) 或對照組(DMSO) 加到復制孔中，DMSO終濃度為0.1%。隨后加入AT9283，集落生長10和14天，計算最佳離散菌落數。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 結晶紫中染色。計算每孔中集落數。使用Prism Graphpad 軟件繪制IC50曲線，通過S形劑量反應曲線計算IC50值。 |
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| 實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | PMID |
| Growth inhibition assay | Cell viability |
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21430070 | |
| 體內研究(In Vivo) | ||
| 體內研究活性 | AT9283 按15 mg/kg和 20 mg/kg劑量作用于攜帶HCT116人結腸癌移植瘤的小鼠，持續(xù)16天，顯著抑制腫瘤生長，抑制分別達67%和76%。此外, 與血漿(半衰期為0.5小時)相比，AT9283口服給藥小鼠，也具有顯著較長的半衰期。[1] |
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|---|---|---|
| 動物實驗 | Animal Models | 后腿側皮下注射HCT116細胞的雄性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 |
化學信息&溶解度
| 分子量 | 381.43 | 分子式 | C19H23N7O2 |
| CAS號 | 896466-04-9 | SDF | Download AT9283 SDF |
| Smiles | C1CC1NC(=O)NC2=C(NN=C2)C3=NC4=C(N3)C=C(C=C4)CN5CCOCC5 | ||
| 儲存條件(自收到貨起) | |||
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體外溶解度 |
DMSO : 76 mg/mL ( (199.25 mM) ；DMSO吸濕會降低化合物溶解度，請使用新開封DMSO) Ethanol : 25 mg/mL (65.54 mM) Water : Insoluble |
摩爾濃度計算器 |
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體內溶解度 現(xiàn)配現(xiàn)用，請按從左到右的順序依次添加，澄清后再加入下一溶劑 |
動物體內配方計算器 | ||||
實驗計算
動物體內配方計算器（澄清溶液）
第一步：請輸入基本實驗信息（考慮到實驗過程中的損耗，建議多配一只動物的藥量）
mg/kg
g
μL
只
第二步：請輸入動物體內配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請聯(lián)系Selleck為您提供正確的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
計算結果：
工作液濃度： mg/ml；
DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過該批次藥物DMSO溶解度，請先聯(lián)系Selleck）；
體內配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH2O，混勻澄清。
體內配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。
注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。
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