Eprenetapopt (APR-246)
别名: PRIMA-1MET
Eprenetapopt (APR-246, PRIMA-1MET)是一种小分子有机化合物，可以恢复肿瘤抑制功能，主要靶向 突变型p53 ，在多种癌细胞类型中诱导细胞死亡。APR-246 可诱导凋亡和自噬。
Eprenetapopt (APR-246) Chemical Structure
CAS: 5291-32-7
客户使用Selleck的发表文献17篇
产品质控
Eprenetapopt (APR-246)相关产品
相关信号通路图
p53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 |
|---|---|---|---|---|---|
| SKBR3 | Cell cycle assay | 5 µM | 2 weeks | lapatinib in combination with APR-246 caused a lower level of G1 arrest and an increase in the sub-G1 fraction | 30743996 |
| UMSCC10A | Cell viability assay | 0-50 μM | 72 h | suppressed cell survival and bore a modest effect on the killing of HNSCC cells | 29348462 |
| FaDu | Cell viability assay | 0-50 μM | 72 h | suppressed cell survival and bore a modest effect on the killing of HNSCC cells | 29348462 |
| MDA-MB-468 | Cell viability assay | IC50=5 μM | 30196236 | ||
| BT549 | Cell viability assay | IC50=3.1 μM | 30196236 | ||
| RS4;11 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| KOPN-8 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| MUTZ-5 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| EU-3 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| UoCB-6 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| NALM-6 | Cell viability assay | high sensitivity and cell death induction in all TP53mut leukemias, but low APR-246 sensitivity in TP53wt ALL | 31073076 | ||
| MDA-MB-231 | Cell viability assay | IC50=4.1 μM | 30196236 | ||
| HCC1143 | Cell viability assay | IC50=6.8 μM | 30196236 | ||
| MDA-MB-453 | Cell viability assay | IC50=0.9 μM | 30196236 | ||
| SKBR3 | Cell viability assay | IC50=5.1 μM | 30196236 | ||
| UACC812 | Cell viability assay | IC50=11.3 μM | 30196236 | ||
| MCF7 | Cell viability assay | IC50=31.1 μM | 30196236 | ||
| MCF10A | Cell viability assay | IC50=5.2 μM | 30196236 | ||
| 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 | ||
| 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 | ||
| 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 | ||
| OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 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 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Eprenetapopt (APR-246, PRIMA-1MET)是一种小分子有机化合物，可以恢复肿瘤抑制功能，主要靶向 突变型p53 ，在多种癌细胞类型中诱导细胞死亡。APR-246 可诱导凋亡和自噬。 | |
|---|---|---|
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | APR-246 (PRIMA-1MET)是处于临床一期的化合物，能够恢复突变型p53的活性，并诱导凋亡。APR-246是一种前体药物，能够转化为活性化合物methylene quinuclidinone (MQ, 一种Michael 受体，通过半胱氨酸与突变型p53结合并恢复p53野生型构象）。在耐药性卵巢癌细胞中，APR-246能够完全恢复p53突变体对cisplatin和doxorubicin的敏感性。它不仅重激活p53，也能以剂量依赖方式降低细胞内谷胱甘肽的水平。APR-246通过诱导ROS、ER胁迫和抑制TrxR1，引起p53依赖性细胞凋亡。在骨髓癌细胞中，APR-246通过破坏GSH/ROS的平衡，不受p53的影响下，诱导细胞凋亡[1]。PRIMA-1Met/APR-246在体内能够有效地抑制表达突变型p53的SCLC细胞的生长并诱导期凋亡，DNA片段化增多、caspase-3激活、PARP分裂、Bax和Noxa上调、Bcl-2下调[2]。 | |||
|---|---|---|---|---|
| 细胞实验 | 细胞系 | OVCAR-3细胞 | ||
| 浓度 | 40 μM | |||
| 孵育时间 | 20 h | |||
| 方法 | 将OVCAR-3细胞以75000细胞每孔的密度接种于12孔板，每孔3 ml培养基。第二天，移除其中2.5 ml培养基，用cisplatin或APR-246或两者结合处理细胞20小时。24小时后，收集细胞，胰蛋白酶化后洗涤两次，用Annexin V and propidium iodine (PI)染色，进行流式分析。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | FL-PARP / Cleaved PARP p-p53 |
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26452133 | |
| Growth inhibition assay | Cell viability |
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| 体内研究(In Vivo) | ||
| 体内研究活性 | APR-246在临床治疗恶性血液病和前列腺癌的1期和2期的剂量探索研究中，展示了其良好的安全性。在动物实验中，APR-246同样也具有良好耐受性，在携带A2780-CP20移植瘤的小鼠中，APR-246的单次给药能够抑制肿瘤生长，生长率下降了21%[1]。 | |
|---|---|---|
| 动物实验 | Animal Models | CD-1 Nu/Nu小鼠 |
| Dosages | 400 mg/kg/天 | |
| Administration | 静脉注射 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT04383938 | Completed | Bladder Cancer|Gastric Cancer|Non Small Cell Lung Cancer|NSCLC|Urothelial Carcinoma|Advanced Solid Tumor |
Aprea Therapeutics |
June 25 2020 | Phase 1|Phase 2 |
| NCT04214860 | Completed | Myeloid Malignancy |
Aprea Therapeutics |
December 13 2019 | Phase 1 |
| NCT03391050 | Terminated | Melanoma |
Aprea Therapeutics|Jules Bordet Institute |
January 18 2018 | Phase 1|Phase 2 |
| NCT02999893 | Terminated | Oesophageal Carcinoma |
Peter MacCallum Cancer Centre Australia |
April 11 2017 | Phase 1|Phase 2 |
化学信息&溶解度
| 分子量 | 199.25 | 分子式 | C10H17NO3 |
| CAS号 | 5291-32-7 | SDF | Download Eprenetapopt (APR-246) SDF |
| Smiles | COCC1(C(=O)C2CCN1CC2)CO | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 40 mg/mL ( (200.75 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : 40 mg/mL (200.75 mM) Ethanol : 40 mg/mL (200.75 mM) |
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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