Eprenetapopt (APR-246)

目录号:S7724 别名: PRIMA-1MET

仅限科研使用

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

规格 价格 库存 购买数量
RMB 795.04 现货
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客户使用Selleck生产的Eprenetapopt (APR-246)发表文献9篇:

产品安全说明书

p53抑制剂选择性比较

相关p53产品

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
Mutant p53 [2]
体外研究

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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UoCB-6 M3jT[GNmdGxidnnhZoltcXS7IHHzd4F6 MUXobYdpKHOnboPpeIl3cXS7IHHu[EBk\WyuIHTlZZRpKGmwZIXjeIlwdiCrbjDhcIwhXFB3M331eEBt\XWtZX3pZZMtKGK3dDDsc5chSVCULUK0OkB{\W6|aYTpeol1gSCrbjDUVFU{f3RiQVzM NUXvbYE2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{GwO|MxPzZpPkOxNFc{ODd4PD;hQi=>
EU-3 MkXKR4VtdCC4aXHibYxqfHliYYPzZZk> NGP5OIRpcWeqIIPlcpNqfGm4aYT5JIFv\CClZXzsJIRm[XSqIHnu[JVkfGmxbjDpckBidGxiVGC1N412fCCuZYXr[Y1q[XNuIHL1eEBtd3diQWDSMVI1PiC|ZX7zbZRqfmm2eTDpckBVWDV|d4SgRWxN MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTB5M{C3Okc,OzFyN{OwO|Y9N2F-
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KOPN-8 MVrD[YxtKH[rYXLpcIl1gSCjc4PhfS=> M3jNWYhq\2hic3Xud4l1cX[rdImgZY5lKGOnbHyg[IVifGhiaX7keYN1cW:wIHnuJIFtdCCWUEWzcZV1KGyndXvlcYlieyxiYoX0JIxwfyCDUGKtNlQ3KHOnboPpeIl3cXS7IHnuJHRRPTO5dDDBUGw> MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{OTB5M{C3Okc,OzFyN{OwO|Y9N2F-
RS4;11 M17mNmNmdGxidnnhZoltcXS7IHHzd4F6 MWTobYdpKHOnboPpeIl3cXS7IHHu[EBk\WyuIHTlZZRpKGmwZIXjeIlwdiCrbjDhcIwhXFB3M331eEBt\XWtZX3pZZMtKGK3dDDsc5chSVCULUK0OkB{\W6|aYTpeol1gSCrbjDUVFU{f3RiQVzM NGnXfWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MUC3N|A4Pid-M{GwO|MxPzZ:L3G+
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HCC1143 NGO4blJE\WyuII\pZYJqdGm2eTDhd5NigQ>? NWrZZpVOUUN3ME22Mlgh|ryP NYrocnVXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CxPVYzOzZpPkOwNVk3OjN4PD;hQi=>
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BT-37 Ml;ZdWhVWyCjc4PhfS=> MkXHdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy| NH\RfmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
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NB1643 M2PTRpFJXFNiYYPzZZk> MkTMdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?= NXj0NVBxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5 MmPmdWhVWyCjc4PhfS=> NE\aU4tyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO= Ml:3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 MofIdWhVWyCjc4PhfS=> NY[2UGJmeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
OHS-50 NGDES2VyUFSVIHHzd4F6 MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy| MoDyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R) NEDOOJhyUFSVIHHzd4F6 NEi4SnByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTVegOlMhMDZvVFegVkkh[2WubIO= NHjmdlg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Rh41 MYnxTHRUKGG|c3H5 MW\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>? MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot FL-PARP / Cleaved PARP p-p53 26452133
Growth inhibition assay Cell viability 26452133
体内研究 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]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

细胞实验:

[1]

  • Cell lines: OVCAR-3细胞
  • Concentrations: 40 μM
  • Incubation Time: 20 h
  • Method:

    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。

动物实验:

[1]

  • Animal Models: CD-1 Nu/Nu小鼠
  • Dosages: 400 mg/kg/天
  • Administration: 静脉注射

溶解度(25°C)

体外

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 199.25
化学式

C10H17NO3

CAS号 5291-32-7
储存条件 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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

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,: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: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: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。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04383938 Completed Drug: APR-246 (eprenetapopt) + Pembrolizumab 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 Drug: APR-246|Drug: Venetoclax|Drug: Azacitidine Myeloid Malignancy Aprea Therapeutics December 13 2019 Phase 1
NCT03391050 Terminated Drug: APR-246|Drug: Dabrafenib Melanoma Aprea Therapeutics|Jules Bordet Institute January 18 2018 Phase 1|Phase 2
NCT02999893 Terminated Drug: APR-246 Oesophageal Carcinoma Peter MacCallum Cancer Centre Australia April 11 2017 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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