Birabresib (OTX015)

别名: MK 8628 中文名称:比拉瑞塞

Birabresib (OTX015, MK 8628) 是一种有效的BET bromodomain抑制剂,在无细胞试验中对BRD2,BRD3,和BRD4的EC50范围为10 到 19 nM。Birabresib 可抑制 Nuclear receptor binding SET domain protein 3 (NSD3) 的靶基因表达。

Birabresib (OTX015) Chemical Structure

Birabresib (OTX015) Chemical Structure

CAS: 202590-98-5

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1613.43 现货
2mg RMB 647.01 现货
10mg RMB 1941.03 现货
100mg RMB 9582.3 现货
1g RMB 16134.3 现货
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客户使用Selleck的Birabresib (OTX015)发表文献67

产品质控

批次: 纯度: 99.9%
99.81

Birabresib (OTX015)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
MV4-11 Cell cycle assay 125 nM 24 hrs Cell cycle arrest in human MV4-11 cells assessed as increase in accumulation at G1-phase at 125 nM measured after 24 hrs by propidium iodide staining based flow cytometry 32208600
MV4-11 Function assay 500 nM 6 to 24 hrs Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc expression at 500 nM measured after 6 to 24 hrs by Western blot analysis 32208600
MV4-11 Function assay 31.25 to 125 nM 6 hrs Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis 32208600
MV4-11 Function assay 31.25 to 125 nM 6 hrs Inhibition of BRD4 in human MV4-11 cells assessed as reduction in BCL2 mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis 32208600
MV4-11 Function assay 31.25 to 125 nM 6 hrs Inhibition of BRD4 in human MV4-11 cells assessed as reduction in CDK6 mRNA level at 31.25 to 125 nM measured after 6 hrs by SYBR green dye based RT-qPCR analysis 32208600
MV4-11 Function assay 10 to 100 nM 24 hrs Inhibition of BRD4 in human MV4-11 cells assessed as reduction in c-Myc mRNA level at 10 to 100 nM after 24 hrs by real time qPCR analysis 31490070
RKO Cell cycle assay 100 nM 24 hrs Induction of cell cycle arrest in human RKO cells assessed as increase in accumulation at G1 phase at 100 nM after 24 hrs by propidium iodide staining based flow cytometric analysis 31490070
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=0.004μM. 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=0.0054μM. 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=0.006μM. 26080064
MM1S Antiproliferative assay 72 hrs Antiproliferative activity against human MM1S cells after 72 hrs by CCK8 or SRB assay, IC50=0.0063μM. 31490070
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=0.0107μM. 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=0.0109μM. 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=0.0166μM. 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=0.0166μM. 26080064
MV4-11 Antiproliferative assay 4 days Antiproliferative activity against human MV4-11 cells assessed as cell growth inhibition after 4 days by CCK8 assay, IC50=0.0176μM. 31461688
MM1S Antiproliferative assay 4 days Antiproliferative activity against human MM1S cells assessed as cell growth inhibition after 4 days by CCK8 assay, IC50=0.0227μM. 31461688
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=0.0255μM. 26080064
BL21(DE3) Function assay 4 hrs Displacement of 5-FITC labelled (+)-JQ1 from His6-tagged human BRD4 bromodomain 1 expressed in Escherichia coli BL21(DE3) )-codon plus-RIL cells incubated for 4 hrs in dark condition by fluorescence anisotropy binding assay, IC50=0.0343μM. 31490070
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.0463μM. 32208600
Kasumi-1 Antiproliferative assay 72 hrs Antiproliferative activity against human Kasumi-1 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.135μM. 32208600
MM1S Antiproliferative assay 72 hrs Antiproliferative activity against human MM1S cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.137μM. 32208600
RS4:11 Antiproliferative assay 72 hrs Antiproliferative activity against human RS4:11 cells assessed as reduction in cell viability measured after 72 hrs by Celltitre-glo luminescence assay, IC50=0.416μM. 32208600
TY82 Antiproliferative assay 72 hrs Antiproliferative activity against human TY82 cells after 72 hrs by CCK8 or SRB assay 31490070
MV4-11 Antiproliferative assay 72 hrs Antiproliferative activity against human MV4-11 cells after 72 hrs by CCK8 or SRB assay 31490070
MV4-11 Apoptosis assay 24 hrs Induction of apoptosis in human MV4-11 cells after 24 hrs by Annexin V staining based assay 31490070
THP1 Antiproliferative assay Antiproliferative activity against human THP1 cells, IC50=0.033μM. 28939121
TY82 Antiproliferative assay Antiproliferative activity against human TY82 cells, IC50=0.067μM. 28939121
insect cells Function assay Inhibition of recombinant full length human N-terminal His6-tagged BRD4 (2 to 1362 residues) expressed in baculovirus infected insect cells using histone H4 peptide as substrate by alpha screen assay, IC50=0.092μM. 30529546
LNCAP Antiproliferative assay Antiproliferative activity against human LNCAP cells, IC50=0.1114μM. 29758518
点击查看更多细胞系数据

生物活性

产品描述 Birabresib (OTX015, MK 8628) 是一种有效的BET bromodomain抑制剂,在无细胞试验中对BRD2,BRD3,和BRD4的EC50范围为10 到 19 nM。Birabresib 可抑制 Nuclear receptor binding SET domain protein 3 (NSD3) 的靶基因表达。
特性 口服生物可利用的BRD2/3/4选择性抑制剂,处于临床I期临床试验,用于治疗血液学恶性肿瘤。
靶点
BRDs [1]
(Cell-free assay)
10-19 nM(EC50)
体外研究(In Vitro)
体外研究活性 OTX015抑制BRD2,BRD3,和BRD4与AcH4的结合,IC50的范围为92到112 nM,并抑制各种人癌细胞系的生长,GI50的范围为60到200 nM。[1] OTX015导致c-MYC表达快速下调,并且在ALKpos ALCL细胞系中,表现出与ALK抑制剂结合的协同抗增殖作用。[2]
激酶实验 TR-FRET 试验[1]
为了评估OTX015与BRD2,BRD3,以及BRD4的结合,BRD表达的CHO细胞裂解物(来自感染表达质粒的CHO细胞, Flag标记的BRD2,BRD3,或BRD4 或仅载体),铕共轭的抗Flag抗体,XL-665共轭的链霉亲和素,和生物素化的OTX015在室温下培育0.2到2小时。荧光性通过TR-FRET使用EnVision 2103多标阅读器测量,结合的EC50使用5.02版PRISM通过非线性回归计算。
细胞实验 细胞系 人肿瘤细胞
浓度 ~2 μM
孵育时间 72小时
方法

OTX015对癌细胞增殖的作用通过将人肿瘤细胞在逐渐增加浓度的OTX015下培育72小时进行评估,并使用基于四唑盐(WST-8)的比色测定评估。

实验图片 检测方法 检测指标 实验图片 PMID
Western blot BRD4 c-Myc JAK2 / p-STAT5 / STAT5 / p-STAT3 / c-Myc / PIM1 / CDK6 / HEXIM1 / p27 / p21 / Bcl-xL / γH2AX ZO-1 / Vimentin 26051217
Immunofluorescence BRD4 Vimentin 28042144
体内研究(In Vivo)
体内研究活性 OTX015(口服)显著抑制Ty82 BRD-NUT中线癌肿瘤在裸鼠体内的生长,100 毫克/千克qd下能够抑制79%,10毫克/千克下抑制61%。[1]
动物实验 Animal Models Ty82 BRD-NUT 中线肿瘤异种移植的BLAB/c-nu/nu小鼠。
Dosages ~100 毫克/千克
Administration 口服
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02698176 Terminated
NUT Midline Carcinoma (NMC)|Triple Negative Breast Cancer (TNBC)|Non-small Cell Lung Cancer (NSCLC)|Castration-resistant Prostate Cancer (CRPC)
Merck Sharp & Dohme LLC
May 4 2016 Phase 1
NCT02698189 Terminated
AML Including AML de Novo and AML Secondary to MDS|DLBCL
Merck Sharp & Dohme LLC
May 19 2016 Phase 1
NCT02296476 Terminated
Glioblastoma Multiforme
Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)
October 29 2014 Phase 2
NCT02259114 Completed
NUT Midline Carcinoma|Triple Negative Breast Cancer|Non-small Cell Lung Cancer With Rearranged ALK Gene/Fusion Protein or KRAS Mutation|Castrate-resistant Prostate Cancer|CRPC|Pancreatic Ductal Adenocarcinoma
Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)
October 23 2014 Phase 1
NCT01713582 Completed
Acute Myeloid Leukemia|Diffuse Large B-cell Lymphoma|Acute Lymphoblastic Leukemia|Multiple Myeloma
Oncoethix GmbH a subsidiary of Merck & Co. Inc. (Rahway New Jersey USA)
December 14 2012 Phase 1

化学信息&溶解度

分子量 491.99 分子式

C25H22ClN5O2S

CAS号 202590-98-5 SDF Download Birabresib (OTX015) SDF
Smiles CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NC4=CC=C(C=C4)O)C5=CC=C(C=C5)Cl)C
储存条件(自收到货起)

体外溶解度
批次:

DMSO : 98 mg/mL ( 199.19 mM; DMSO吸湿会降低化合物溶解度,请使用新开封DMSO)

Ethanol : 98 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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