I-BET151 (GSK1210151A)

I-BET151 (GSK1210151A)是一种新型,选择性的BET抑制剂,作用于BRD2,无细胞试验中BRD3BRD4IC50分别为0.5 μM, 0.25 μM和0.79 μM。

I-BET151 (GSK1210151A) Chemical Structure

I-BET151 (GSK1210151A) Chemical Structure

CAS: 1300031-49-5

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 2121.21 现货
5mg RMB 1382.25 现货
10mg RMB 2231.18 现货
50mg RMB 7130.63 现货
1g RMB 32678.1 现货
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批次: 纯度: 99.99%
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I-BET151 (GSK1210151A)相关产品

Epigenetic Reader Domain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
HT-29 Function assay 0.3125 uM to 5 uM 24 hrs Inhibition of BRD4 in human HT-29 cells assessed as reduction in c-Myc protein expression at 0.3125 uM to 5 uM uM after 24 hrs by Western blotting method 25559428
H929 Apoptosis assay ~1 μM induces cell apoptosis 24335499
RPMI8226 Function assay ~1 μM induces cell cycle arrest 24335499
KMS11 Function assay ~1 μM induces cell cycle arrest 24335499
KMS18 Function assay ~1 μM induces cell cycle arrest 24335499
KMS12BM Function assay ~1 μM induces cell cycle arrest 24335499
KMS12PE Function assay ~1 μM induces cell cycle arrest 24335499
H929 Function assay ~1 μM induces cell cycle arrest 24335499
BC3 Function assay 800 nM reduces c-Myc protein levels 23792448
BC1 Function assay 800 nM reduces c-Myc protein levels 23792448
BC3 Function assay 500 nM induces cell-cycle arrest 23792448
BC1 Function assay 500 nM induces cell-cycle arrest 23792448
UM-PEL-3 Growth inhibitory assay ~1 μM IC50=180 nM 23792448
UM-PEL-1 Growth inhibitory assay ~1 μM IC50=210 nM 23792448
U266 Growth inhibitory assay ~1 μM IC50=950 nM 23792448
MM1S Growth inhibitory assay ~1 μM IC50=760 nM 23792448
Jurkat Growth inhibitory assay ~1 μM IC50=1220 nM 23792448
Namalwa Growth inhibitory assay ~1 μM IC50=970 nM 23792448
BJAB Growth inhibitory assay ~1 μM IC50=970 nM 23792448
BCBL1 Growth inhibitory assay ~1 μM IC50=330 nM 23792448
BC3 Growth inhibitory assay ~1 μM IC50=460 nM 23792448
BC1 Growth inhibitory assay ~1 μM IC50=220 nM 23792448
A72 Function assay ~10 μM reactivates latent HIV-1 23255218
A2 Function assay ~10 μM reactivates latent HIV-1 23255218
MOLM13 Apoptosis assay ~100 μM induces apoptosis 21964340
MV4;11 Apoptosis assay ~100 μM induces apoptosis 21964340
HL60 cytotoxicity assay ~100 μM IC50=890 nM 21964340
MEG01 cytotoxicity assay ~100 μM IC50=25 μM 21964340
K562 cytotoxicity assay ~100 μM IC50>100 μM 21964340
HEL cytotoxicity assay ~100 μM IC50=1 μM 21964340
NOMO1 cytotoxicity assay ~100 μM IC50=15 nM 21964340
MOLM13 cytotoxicity assay ~100 μM IC50=120 nM 21964340
RS4;11 cytotoxicity assay ~100 μM IC50=192 nM 21964340
MV4;11 cytotoxicity assay ~100 μM IC50=26 nM 21964340
KMS12PE Apoptosis assay ~1 μM induces cell apoptosis 24335499
KMS12BM Apoptosis assay ~1 μM induces cell apoptosis 24335499
KMS18 Apoptosis assay ~1 μM induces cell apoptosis 24335499
KMS11 Apoptosis assay ~1 μM induces cell apoptosis 24335499
RPMI8226 Apoptosis assay ~1 μM induces cell apoptosis 24335499
U87MG Function assay ~10 μM reduces U87MG cellular ATP with IC50 of 1.05 μM 24496381
A172 Function assay ~10 μM reduces cellular ATP with IC50 of 1.28 μM 24496381
SW1783 Function assay ~10 μM reduces cellular ATP with IC50 of 2.68 μM 24496381
U87MG Function assay ~10 μM increases proportion of cells in the G1/S transition 24496381
RAW267.4 Function assay 1 μM reduces IL-6 production induced by LPS 24859008
RAW267.4 Function assay 1 μM reduces the association between BRD4 and acetylated p65 24859008
Me007 Growth inhibitory assay ~100 μM inhibits the growth 24906137
SK-Mel-28 Growth inhibitory assay ~100 μM inhibits the growth 24906137
Mel-RMU Growth inhibitory assay ~100 μM inhibits the growth 24906137
Mel-JD Growth inhibitory assay ~100 μM inhibits the growth 24906137
Mel-RM Growth inhibitory assay ~100 μM inhibits the growth 24906137
Me007 Apoptosis assay ~100 μM induces apoptosis 24906137
SK-Mel-28 Apoptosis assay ~100 μM induces apoptosis 24906137
Mel-RMU Apoptosis assay ~100 μM induces apoptosis 24906137
Mel-JD Apoptosis assay ~100 μM induces apoptosis 24906137
Mel-RM Apoptosis assay ~100 μM induces apoptosis 24906137
Me007 Function assay 10 μM induces cell cycle arrest by upregulation of p21 24906137
SK-Mel-28 Function assay 10 μM induces cell cycle arrest by upregulation of p21 24906137
Mel-RMU Function assay 10 μM induces cell cycle arrest by upregulation of p21 24906137
Mel-JD Function assay 10 μM induces cell cycle arrest by upregulation of p21 24906137
Mel-RM Function assay 10 μM induces cell cycle arrest by upregulation of p21 24906137
Me007 Function assay 10 μM upregulates proapoptotic and cell cycle arrest genes 24906137
SK-Mel-28 Function assay 10 μM upregulates proapoptotic and cell cycle arrest genes 24906137
Mel-RMU Function assay 10 μM upregulates proapoptotic and cell cycle arrest genes 24906137
Mel-JD Function assay 10 μM upregulates proapoptotic and cell cycle arrest genes 24906137
Mel-RM Function assay 10 μM upregulates proapoptotic and cell cycle arrest genes 24906137
HepG2 Function assay 18 hrs Upregulation of ApoA1 expression in human HepG2 cells assessed as concentration required to increase 70% of luciferase activity after 18 hrs by luciferase reporter gene assay, EC170 = 0.09 μM. 22386529
Raji Function assay 4 hrs Inhibition of BRD4 in human Raji cells assessed as reduction of MYC expression after 4 hrs, IC50 = 0.13 μM. 24900758
MV4-11 Growth inhibition assay 72 hrs Growth inhibition of human MV4-11 cells after 72 hrs by SRB assay, IC50 = 0.119 μM. 25559428
MM1S Growth inhibition assay 72 hrs Growth inhibition of human MM1S cells after 72 hrs by SRB assay, IC50 = 0.299 μM. 25559428
HT-29 Growth inhibition assay 72 hrs Growth inhibition of human HT-29 cells after 72 hrs by SRB assay, IC50 = 0.945 μM. 25559428
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.0317 μM. 26080064
MV4-11 Cytotoxicity assay 4 days Cytotoxicity against human MV4-11 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.162 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, IC50 = 0.226 μM. 26080064
MOLM13 Cytotoxicity assay 4 days Cytotoxicity against human MOLM13 cells harboring MLL1 fusion gene assessed as growth inhibition after 4 days by CellTiter-Glo luminescent assay, IC50 = 0.228 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.0317 μM. 28463487
MV4-11 Growth inhibition assay 4 days Growth inhibition of human MV4-11 cells after 4 days by WST-8 assay, IC50 = 0.162 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, IC50 = 0.226 μM. 28463487
MOLM13 Growth inhibition assay 4 days Growth inhibition of human MOLM13 cells after 4 days by WST-8 assay, IC50 = 0.228 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0072 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.009 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.009 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0223 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0496 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Displacement of FAM-labeled ZBA248 from BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay, Ki = 0.0748 μM. 26080064
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.009 μM. 28463487
Rosetta2 DE3 Function assay 30 mins Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 2 (333 to 460 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay, Ki = 0.0748 μM. 28463487
PBMC Function assay inhibits IL-6 with pIC50 of 6.7 22437115
MV4;11 Function assay decreases the recruitment of BRD3/4 and impaired recruitment of CDK9 and PAF1 to the transcriptional start site 21964340
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD3 BD1 (24 to 144 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0298 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0405 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD4 BD1 (44 to 168 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0528 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD2 BD1 (72 to 205 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0548 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD2 BD2 (349 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.0703 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated BRD4 BD2 (333 to 460 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 0.215 μM. 26080064
Rosetta2 DE3 Function assay Binding affinity to biotinylated CREBBP (1043 to 1159 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells by bio-layer interferometry method, Kd = 3.084 μM. 26080064
THP1 Antiinflammatory assay Antiinflammatory activity in human THP1 cells 22386529
MV4-11 Function assay Inhibition of BRD4 in human MV4-11 cells assessed as downregulation of BCL2 RNA expression by RNA-seq analysis 29259751
MV4-11 Function assay Inhibition of BRD4 in human MV4-11 cells assessed as downregulation of cMYC RNA expression by RNA-seq analysis 29259751
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
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
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
Rh30 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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
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
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
点击查看更多细胞系数据

生物活性

产品描述 I-BET151 (GSK1210151A)是一种新型,选择性的BET抑制剂,作用于BRD2,无细胞试验中BRD3BRD4IC50分别为0.5 μM, 0.25 μM和0.79 μM。
特性 优化I-BET151,使其有效及选择性靶向作用于BET,同时增强体内药代动力学和终末半衰期,以使延长体内研究。
靶点
BRD3 [1]
(Cell-free assay)
BRD2 [1]
(Cell-free assay)
BRD4 [1]
(Cell-free assay)
0.25 μM 0.5 μM 0.79 μM
体外研究(In Vitro)
体外研究活性 I-BET151有效,选择性作用于多种不同蛋白类型,如COX-2, P450, Aurora B, GSK3β, PI3K-γ, GPCR, 离子通道,转运体。与I-BET762 (GSK525762A)类似, I-BET151 对BRD2, BRD3 和BRD4具有高的结合亲和力,Kd为0.02-0.1 μM,作用于人类外周血单核细胞(PBMC)和全血(WB)以及大鼠WB,显著抑制脂多糖刺激的IL-6细胞因子产生,IC50分别为0.16 μM, 1.26 μM, 和 1.26 μM。I-BET151(0.5 or 5 μM)作用于HL60核提取物,抑制BETs(BRD2, BRD3, BRD4, 和 BRD9)而非23种其他溴区蛋白结合到乙酰化的组蛋白肽。I-BET151有效作用于含不同 MLL融合的细胞系,如MV4;11, RS4;11, MOLM13, 和NOMO1 细胞, IC50为15-192 nM。一致的是,I-BET151完全消除MLL融合驱动的白血病(MOLM13)而非酪氨酸激酶激活(K562)驱动的白血病的菌落形成潜力。I-BET151也有效作用于液体培养和转化MLL-ENL或MLL-AF9的原代小鼠祖细胞的克隆形成实验。I-BET151作用于由不同的MLL融合(分别含MLL-AF9和MLL-AF4的MOLM13和MV4;11)而非K562细胞驱动的MLL融合细胞系,显著诱导细胞凋亡和G0/G1期停滞,可能是由于通过抑制BRD3/4,PAFc和SEC组分招募到转录起始位点(TSS),而抑制BCL-2,C-MYC和CDK6的转录。[1]
激酶实验 荧光各向异性(FP)的配体位移检测
所有组分溶解在50 mM HEPES pH 7.4, 150 mM NaCl和 0.5 mM CHAPS组成的Buffer中,BRD 2/3/4终浓度为75 nM,荧光配体为5 nM。在Greiner 384孔黑色的低量微孔板中,使用Micro Multidrop 将10 μL反应混合物加入到含100 nL各种浓度I-BET151或DMSO空白对照(1%最终)的孔中,并在黑暗中室温下平衡60分钟。使用 Envision (lex=485 nm,lEM=530 nm;Dichroic=505 nM)读取荧光各向异性。
细胞实验 细胞系 MV4;11, MOLM13, NOMO1, RS4;11, HEL, HL60 和 K562
浓度 溶于DMSO, 终浓度为~100 μM
孵育时间 24,或72小时
方法

使用多种不同浓度I-BET151在384孔或96孔板中处理细胞24或72小时。细胞生长抑制实验中,实验板每孔中加入与细胞培养基同等体积的CellTiter-Glo试剂,震荡约2分钟,然后在Analyst GT 或EnVision酶标仪上读取化学发光信号。细胞增殖实验中,每孔加入CellTiter-Aqueous One,然后实验板在37°C下温育4小时。在SpectraMax Gemini酶标仪上490 nm处读取吸光度。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot HP1α / HP1β / HP1γ FoxM1 / AURKB / Survivin / cyclin B / PLK1 α-SMA / Fibronectin / Collagen-1 30386240
体内研究(In Vivo)
体内研究活性 I-BET151每天按30 mg/kg剂量处理小鼠,显著抑制鼠类MLL-AF9和人类MLL-AF4白血病肿瘤生长,显著延长寿命。[1]
动物实验 Animal Models 静脉注射MV4;11细胞的NOD-SCID小鼠,静脉注射MLL-AF9细胞的C57BL/6小鼠
Dosages ~30 mg/kg/day
Administration 腹腔注射

化学信息&溶解度

分子量 415.44 分子式

C23H21N5O3

CAS号 1300031-49-5 SDF Download I-BET151 (GSK1210151A) SDF
Smiles CC1=C(C(=NO1)C)C2=C(C=C3C(=C2)N=CC4=C3N(C(=O)N4)C(C)C5=CC=CC=N5)OC
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 83 mg/mL ( (199.78 mM); DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 83 mg/mL

Water : Insoluble

摩尔浓度计算器

体内溶解度
批次:

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

摩尔浓度计算器

质量 浓度 体积 分子量

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。

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