Onalespib (AT13387)
Onalespib (AT13387)是一种有效的，选择性Hsp90抑制剂，在A375细胞中IC50为18 nM，具有长持续性抗肿瘤活性。Phase 2。
Onalespib (AT13387) Chemical Structure
CAS: 912999-49-6
客户使用Selleck的Onalespib (AT13387)发表文献28篇
客户使用该产品的3个实验数据
产品质控
Onalespib (AT13387)相关产品
相关信号通路图
HSP (HSP90)抑制剂选择性比较
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 |
|---|---|---|---|---|---|
| human HCT116 cells | Function assay | 30 nM | 18 h | Induction of apoptosis in human HCT116 cells assessed as reduction of Raf-1 level at 30 nM after 18 hrs by immunoblotting | 20662534 |
| human HCT116 cells | Function assay | 30 nM | 18 h | Induction of apoptosis in human HCT116 cells assessed as reduction of CDK4 level at 30 nM after 18 hrs by immunoblotting | 20662534 |
| human HCT116 cells | Function assay | 10 nM | 18 h | Induction of apoptosis in human HCT116 cells assessed as upregulation of Hsp70 level at 10 nM after 18 hrs by immunoblotting | 20662534 |
| PANC1 | Function assay | 1 uM | 36 hrs | Inhibition of HSP90alpha in human PANC1 cells assessed as up-regulation of Hsp70 at 1 uM after 36 hrs by Western blot analysis | 30351001 |
| PANC1 | Function assay | 1 uM | 36 hrs | Inhibition of HSP90alpha in human PANC1 cells assessed as akt degradation at 1 uM after 36 hrs by Western blot analysis | 30351001 |
| human HCT116 cells | Proliferation assay | 48 h | Antiproliferative activity against human HCT116 cells after 48 hrs by MTT assay, IC50=0.08 μM | 24763261 | |
| human SKBR3 cells | Proliferation assay | 48 h | Antiproliferative activity against human SKBR3 cells after 48 hrs by MTT assay, IC50=0.14 μM | 24763261 | |
| human MCF7 cells | Proliferation assay | 48 h | Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=0.28 μM | 24763261 | |
| human A231 cells | Proliferation assay | 48 h | Antiproliferative activity against human A231 cells after 48 hrs by MTT assay, IC50=1.01 μM | 24763261 | |
| GIST430 | Cytotoxicity assay | 7 days | Cytotoxicity against imatinib-resistant human GIST430 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.034μM. | 26844689 | |
| GIST48 | Cytotoxicity assay | 7 days | Cytotoxicity against imatinib-resistant human GIST48 cells assessed as decrease in cell viability after 7 days by alamar blue assay, IC50=0.055μM. | 26844689 | |
| MCF7 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MCF7 cells incubated for 72 hrs by MTT assay, IC50=0.032μM. | 29028527 | |
| SKBR3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SKBR3 cells incubated for 72 hrs by MTT assay, IC50=0.045μM. | 29028527 | |
| NCI-H3122 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB assay, IC50=0.052μM. | 29698859 | |
| MCF7 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50=0.29μM. | 30784881 | |
| NCI-H1299 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human NCI-H1299 cells after 72 hrs by MTT assay, IC50=0.37μM. | 30784881 | |
| A549 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50=0.44μM. | 30784881 | |
| Vero E6 | Function assay | 48 hrs | IC50 for antiviral activity against SARS-CoV-2 in the Vero E6 cell line at 48 h by immunofluorescence-based assay (detecting the viral NP protein in the nucleus of the Vero E6 cells), IC50=0.15488μM. | 32353859 | |
| human HCT116 cells | Cytotoxic assay | Cytotoxicity against human HCT116 cells by Alamar blue assay, IC50=0.048 μM | 20662534 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| 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 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 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 | ||
| 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 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells | 29435139 | ||
| LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells | 29435139 | ||
| BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells | 29435139 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells | 29435139 | ||
| SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Onalespib (AT13387)是一种有效的，选择性Hsp90抑制剂，在A375细胞中IC50为18 nM，具有长持续性抗肿瘤活性。Phase 2。 | ||
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| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | AT13387抑制多种激酶，包括 CDK 1, CDK 2, CDK4, FGFR3, PKB-b, JAK2, VEGFR2, PDGFR-b ，和Aurora B。但是AT13387浓度低于30 μM时对实验激酶没有明显抑制效果。AT13387 有效抑制多种肿瘤细胞系(如 MES-SA 细胞系)增殖和存活。AT13387作用于一组30个肿瘤细胞系，有效抑制细胞增殖，GI50值为13-260 nM。AT13387抑制非致瘤性前列腺上皮细胞系PNT2增殖，GI50值为480 nM。[2] | |||
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| 激酶实验 | HSP90竞争等温热量测定 | |||
| 竞争等温热量测定(ITC)格式测定AT13387与HSP90结合的Kd值。ITC 实验在Micro Cal VP-ITC上 25oC下进行，实验buffer含 25 mM Tris, 100 mM NaCl, 1 mM MgCl2 和 1 mM Tris(2-羧乙基) 磷化氢，pH 为7.4，为了获得高亲和力。 | ||||
| 细胞实验 | 细胞系 | A375, 22RV1, T474 | ||
| 浓度 | 1 μM | |||
| 孵育时间 | 4小时 | |||
| 方法 | A375, 22RV1, T474, DU1 45, LNCa P, MCF-7, DA-MB-468 细胞系接种在96孔板上，然后加入溶于0.1% (v/v)DMSO的AT13387。使用10孔剂量反应曲线，测定GI50值，重复2次。然后加入Alamar blueis，细胞再温育4小时，然后读取荧光值。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | HSP90 / HSP70 EGFR / p-EGFR / AKT / p-AKT / ERK / p-ERK / S6 / p-S6 AXL / c-Myc / p-Mnk1 / Mnk1 / p-eIF4E / eIF4E |
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| Growth inhibition assay | Cell viability |
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28679777 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | AT13387按70 mg/kg剂量每周处理两次，或者按90 mg/kg剂量每周处理一次。鼠体重降低不超过20%。非治疗期延长，及抗癌活性，与AT13387作用于突变EGFR和其他生物标签的长期药效，及AT13387对肿瘤的记忆有关。[2] | |
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| 动物实验 | Animal Models | 无胸腺BALB /c鼠 |
| Dosages | 80 mg/kg | |
| Administration | 腹腔注射 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02898207 | Completed | Metastatic High Grade Fallopian Tube Serous Adenocarcinoma|Metastatic Malignant Solid Neoplasm|Metastatic Primary Peritoneal Serous Adenocarcinoma|Metastatic Triple-Negative Breast Carcinoma|Platinum-Resistant Fallopian Tube Carcinoma|Platinum-Resistant Ovarian Carcinoma|Platinum-Resistant Primary Peritoneal Carcinoma|Recurrent Breast Carcinoma|Recurrent High Grade Fallopian Tube Serous Adenocarcinoma|Recurrent High Grade Ovarian Serous Adenocarcinoma|Recurrent Primary Peritoneal High Grade Serous Adenocarcinoma|Recurrent Triple-Negative Breast Carcinoma|Refractory Fallopian Tube Serous Adenocarcinoma|Refractory Ovarian Serous Adenocarcinoma|Refractory Primary Peritoneal Serous Adenocarcinoma|Refractory Triple-Negative Breast Carcinoma|Unresectable High Grade Fallopian Tube Serous Adenocarcinoma|Unresectable Malignant Solid Neoplasm|Unresectable Primary Peritoneal Serous Adenocarcinoma |
National Cancer Institute (NCI) |
May 19 2017 | Phase 1 |
化学信息&溶解度
| 分子量 | 409.52 | 分子式 | C24H31N3O3 |
| CAS号 | 912999-49-6 | SDF | Download Onalespib (AT13387) SDF |
| Smiles | CC(C)C1=CC(=C(C=C1O)O)C(=O)N2CC3=C(C2)C=C(C=C3)CN4CCN(CC4)C | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 25 mg/mL ( (61.04 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）
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）
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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* 必填项
常见问题及建议解决方法
问题 1:
How to prepare the compound for in vivo studies?
回答：
S1163 AT13387 can be dissolved in 2% DMSO/30% PEG 300/ddH2O at 10 mg/ml as a clear solution. But after stayed for about 1 hour, the precipitation will goes out. So it is recommended to be prepared before use.
