Molibresib (I-BET-762)

目录号:S7189 别名: GSK525762, GSK525762A

仅限科研使用

Molibresib (I-BET-762, GSK525762, GSK525762A) 是一种BET蛋白抑制剂,无细胞试验中IC50约为35 nM,抑制巨噬细胞产生促炎性蛋白质,并抑制急性炎症,对其他溴区结合域包含的蛋白具有高度选择性。

Molibresib (I-BET-762) Chemical Structure

CAS: 1260907-17-2

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 2923.83 现货
RMB 1859.99 现货
RMB 3838.64 现货
大包装 有超大折扣

今日订购,明日送达 全国免运费 分装免费 分装成小规格产品(单支最小为1mg)
如1支10mg产品可分装为10支1mg产品

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Molibresib (I-BET-762)发表文献26篇:

产品安全说明书

Epigenetic Reader Domain抑制剂选择性比较

生物活性

产品描述 Molibresib (I-BET-762, GSK525762, GSK525762A) 是一种BET蛋白抑制剂,无细胞试验中IC50约为35 nM,抑制巨噬细胞产生促炎性蛋白质,并抑制急性炎症,对其他溴区结合域包含的蛋白具有高度选择性。
靶点
BET proteins [1]
(Cell-free assay)
35 nM
体外研究

I-BET-762抑制BET(溴区和额外的末端结构域) 蛋白, BRD2, BRD3 和 BRD4, 结合到BET的串联溴区,Kd为50.5-61.3 nM, 在FRET分析中,置换BET串联溴区的一种四乙酰化的H4肽,IC50为32.5-42.5 nM。I-BET-762占据BET蛋白的乙酰基-赖氨酸结合口袋,并抑制BET蛋白结合到乙酰化的组蛋白,从而破坏了炎性基因表达必不可少的染色质复合物的形成。[1]分化过程中的第2天使用I-BET-762处理,改变CD4+T细胞的细胞因子产生,上调一些抗炎基因产物的表达,并下调一些促炎细胞因子的表达。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HepG2 NH;ze3NHfW6ldHnvckBie3OjeR?= M4\1V|E5KGi{cx?= MYTJcoR2[3Srb36gc4YhcHWvYX6gRZBwSTFiZ3Xu[UBmgHC{ZYPzbY9vKGmwIIP0ZYJtgSC2cnHud4Zm[3SnZDDoeY1idiCKZYDHNkBk\WyuczDjc4V5eHKnc4PpcochdHWlaX\ldoF{\SC{ZYDvdpRmeiCpZX7lJIFnfGW{IEG4JIhzeyCkeTDseY1qdmW|Y3XuZ4Uh[XO|YYmsJGVEPTBiPTCwMlch|ryPLh?= Mm\qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF3NkizNlIoRjJzNU[4N|IzRC:jPh?=
HepG2 NFrGXHhHfW6ldHnvckBie3OjeR?= MlfhOkBpenN? M1;Eemlv\HWldHnvckBw\iCqdX3hckBCeG:DMTDwdo91\WmwIIP5cpRp\XOrczDpckBpfW2jbjDI[ZBIOiClZXzsd{Bie3Onc4Pl[EBieyCwZX;zfY51cGW|aYPl[EBz[WSrb3zhZoVt\WRicILveIVqdiC|ZXPy[ZRqd25iYX\0[ZIhPiCqcoOgZpkhW0SVIGDBS2Uh[W6jbInzbZMhcW5icILld4Vv[2Vib3[gX|M2W12vZYTobY9vcW6n NG\sfHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUW2PFMzOid-MkG1Olg{OjJ:L3G+
HepG2 MXLGeY5kfGmxbjDhd5NigQ>? NEPBZocyQCCqcoO= MknUWZBz\We3bHH0bY9vKG:oIFHwc2EyKGW6cILld5Nqd25iaX6gbJVu[W5iSHXwS|Ih[2WubIOgZZN{\XO|ZXSgZZMh[2:wY3XueJJifGmxbjDy[ZF2cXKnZDD0c{BqdmO{ZXHz[UA4OCVib3[gcJVkcW[ncnHz[UBi[3Srdnn0fUBi\nSncjCxPEBpenNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCHQ{G3NEA:KDBwMjFOwG0v NVWxPYR6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFY2OjlpPkKyN|g3PTJ7PD;hQi=>
HepG2 MlzzSpVv[3Srb36gZZN{[Xl? MnfyNVghcHK| NGf0fW1KdmS3Y4Tpc44hd2ZiaIXtZY4hSXCxQUGg[4Vv\SCneIDy[ZN{cW:wIHnuJJN1[WKueTD0doFve2[nY4Tl[EBpfW2jbjDI[ZBIOiClZXzsd{Bkd2W6cILld5NqdmdibIXjbYZmemG|ZTDy[ZBwenSncjDn[Y5mKGGodHXyJFE5KGi{czDifUBtfW2rbnXzZ4Vv[2ViYYPzZZktKEWFNUCgQUAxNjdizszNMi=> MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{NESzOEc,OjJ7MkS0N|Q9N2F-
PBMC MX3BcpRqcW6obHHtcYF1d3K7IHHzd4F6 NGewTZFCdnSraX7mcIFudWG2b4L5JIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iUFLNR{Bk\WyuczDhd5Nme3OnZDDhd{BNWFNvaX7keYNm\CCLTD22JJBzd2S3Y4Tpc44h[nliY3jlcYltfW2rbnXzZ4Vv[2ViYYPzZZktKEmFNUCgQUAxNjNzNkKzJO69VS5? MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDBzNUm2O{c,OjRyMUW5Olc9N2F-
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TY82 Mm\GSpVv[3Srb36gZZN{[Xl? MUWwMlIhfG9iMTD1US=> M1P2O|I1KGi{cx?= MYfJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gWHk5OiClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ{1OgWNicILveIVqdiCneIDy[ZN{cW:wIHH0JFAvOiC2bzCxJJVOKGGodHXyJFI1KGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN? MkTEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl3MkW0N|UoRjJ7NUK1OFM2RC:jPh?=
TY82 NW[xdotWTnWwY4Tpc44h[XO|YYm= Mn\GNE4zKHSxIEGgeW0> MX6yOEBpenN? MXnJcohq[mm2aX;uJI9nKEKURESgbY4hcHWvYX6gWHk5OiClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ{1OgWNibWLORUBmgHC{ZYPzbY9vKGG2IECuNkB1dyBzIIXNJIFnfGW{IEK0JIhzeyCkeTDSWE1RS1JiYX7hcJl{cXN? MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTV{NUSzOUc,Ojl3MkW0N|U9N2F-
TY82 or NCI-H1299 M2XVdWZ2dmO2aX;uJIF{e2G7 MoXHNE4zKHSxIEGgeW0> NFnjcoIzPCCqcoO= M{nkW2lvcGmkaYTpc44hd2ZiQmLEOEBqdiCqdX3hckBVYTh{IH;yJG5EUS2KMUK5PUBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iUFStUFEheHKxdHXpckBmgHC{ZYPzbY9vKGG2IECuNkB1dyBzIIXNJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> M320TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUK1OFM2Lz5{OUWyOVQ{PTxxYU6=
TY82 or NCI-H1299 MVXGeY5kfGmxbjDhd5NigQ>? NWXFWm1GOC5{IITvJFEhfU1? MlHRNlQhcHK| NHjCWXZKdmirYnn0bY9vKG:oIFLSSFQhcW5iaIXtZY4hXFl6MjDvdkBPS0lvSEGyPVkh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKGmwIGDEMWwyKG2UTlGg[ZhxemW|c3nvckBifCByLkKgeI8hOSC3TTDh[pRmeiB{NDDodpMh[nliUmStVGNTKGGwYXz5d4l{ M37Od|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUK1OFM2Lz5{OUWyOVQ{PTxxYU6=
C4-2B MXjBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M3;N[Vk3KGi{cx?= MVfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEN2LULCJINmdGy|IHHmeIVzKDl4IHjyd{BjgSCFZXzsMXRqfGW{IHfsc{Bz\WGpZX70JIJie2WmIHz1cYlv\XOlZX7j[UBie3OjeR?= NUm3fFR5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1OFE{PzFpPkK5OVQyOzdzPD;hQi=>
22Rv1 NVfsVoFjSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MWW5OkBpenN? NUP6dZV2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjCyNnJ3OSClZXzsd{Bi\nSncjC5OkBpenNiYomgR4VtdC2WaYTldkBodG9icnXh[4VvfCCkYYPl[EBtfW2rbnXzZ4Vv[2ViYYPzZZk> NH61b2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUW0NVM4OSd-Mkm1OFE{PzF:L3G+
LNCAP MW\BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NUDUR5NVQTZiaILz MoKyRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCOTlPBVEBk\WyuczDh[pRmeiB7NjDodpMh[nliQ3XscE1VcXSncjDncI8hemWjZ3XueEBj[XOnZDDseY1qdmW|Y3XuZ4Uh[XO|YYm= NHPqe2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUW0NVM4OSd-Mkm1OFE{PzF:L3G+
HL60 NV;sWJdxS3m2b4TvfIlkcXS7IHHzd4F6 MXTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIUFYxKGOnbHzzJIJ6KE2WUzDhd5NigSxiSVO1NEA:KDBwMUKg{txONg>? NUHZeph3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2OVcxQTlpPkK5OlU4ODl7PD;hQi=>
Raji NVyyPGlsTnWwY4Tpc44h[XO|YYm= M2rEXGlvcGmkaYTpc44hd2ZiQmLEOE1DTDFiaX6gbJVu[W5iUnHqbUBk\WyuczDhd5Nme3OnZDDhd{Bld3ewcnXneYxifGmxbjDv[kBOYUNiZ3Xu[UBmgHC{ZYPzbY9vKGK7IGDDVkBu\XSqb3SsJGlEPTBiPTCwMlE{OiEQvF2u MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ3N{C5PUc,Ojl4NUewPVk9N2F-
LNCAP NU\MbpJvSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MX3BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEyQQ1HQJINmdGy|LDDJR|UxKD1iMD6zOVY2KM7:TT6= MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTd3OEWxPEc,Ojl5NUi1NVg9N2F-
MV411 MX;DfZRwfG:6aXPpeJkh[XO|YYm= MVO3NkBpenN? MknxR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUXY1OTFiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9iYYPzZZktKEmFNUCgQUAxNjhizszNMi=> M4q0VFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMk[4O|AzLz5|MEK2PFcxOjxxYU6=
Assay
Methods Test Index PMID
Growth inhibition assay Cell viability 26840085
体内研究 I-BET-762保护防止脂多糖诱导的内毒素休克和细菌诱导的脓毒病。LPS注射后1.5小时,单剂量I-BET处理,可治愈小鼠。I-BET每日两次注射,持续2天,保护小鼠免于脓毒症引起的死亡。[1]早期I-BET-762处理实验性自身免疫性脑脊髓炎(EAE)小鼠模型,抑制Th1分化的2D2 T细胞诱发神经性炎症的能力。[2]

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)

激酶实验:[1]
  • 荧光共振能量转移(FRET)滴定:

    在有四乙酰化的组蛋白H4肽(200 nM)存在时,在50 mM HEPES pH7.5, 50 mM NaCl, 0.5 mM CHAPS中进行对BRD2 (200 nM), BRD3 (100 nM) 和 BRD4 (50 nM)的I-BET滴定。平衡1小时后,在含0.05% (v/v) BSA 和 400 mM KF的实验缓冲液中加入2nM 铕穴状化合物标记的链霉亲和素和10 nM XL-665标记的anti-6His 抗体,使用FRET检测溴区蛋白:肽相互作用。使用Envision酶标仪(激发菠菜320 nm,发射波长615 nm和665 nm)对实验板进行读数。

细胞实验:[2]
  • Cell lines: CD4+ T 细胞
  • Concentrations: ~500 nM
  • Incubation Time: 60-72 小时
  • Method: 从10到12周的小鼠淋巴结和脾中分离CD4+ T细胞,在指定细胞因子存在时,使用与板结合的anti-CD3和anti-CD28抗体活化。在最初激活的60-72小时,包含I-BET-762化合物。在T细胞培养和扩张的5天过程中,化合物稀释到初始浓度的12倍。
动物实验:[1]
  • Animal Models: 小鼠
  • Dosages: 30 mg/kg
  • 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 423.9
化学式

C22H22ClN5O2

CAS号 1260907-17-2
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
NCT03266159 Withdrawn Drug: GSK525762 Besylate tablets|Drug: Trametinib tablets Solid Tumours GlaxoSmithKline November 27 2017 Phase 2
NCT02964507 Completed Drug: GSK525762|Drug: Placebo|Drug: Fulvestrant Neoplasms GlaxoSmithKline February 2 2017 Phase 1
NCT01943851 Completed Drug: GSK525762 Neoplasms GlaxoSmithKline May 14 2014 Phase 2
NCT01587703 Completed Drug: GSK525762 Carcinoma Midline GlaxoSmithKline March 28 2012 Phase 1

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

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