Birabresib (OTX015)

别名: MK 8628 中文名称：比拉瑞塞

目录号：S7360 Purity: 99.9%

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

CAS: 202590-98-5

规格	价格	库存
10mM (1mL in DMSO)	1613.43	现货
2mg	647.01	现货
10mg	1941.03	现货
100mg	9582.3	现货
1g	16134.3	现货
更大包装有超大折扣
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产品质控

批次：纯度： 99.9%

99.9

Birabresib (OTX015)相关产品

相关靶点	BET p300/CBP BRPF bromodomain	点击展开
相关产品	ICG-001 I-BET151 (GSK1210151A) Molibresib (I-BET-762) SGC-CBP30 EED226 Apabetalone (RVX-208) KG-501 CPI-203 compound 3i (666-15) PFI-3 AZD5153 6-hydroxy-2-naphthoic acid PFI-1 (PF-6405761) Mivebresib (ABBV-075) ABBV-744 UNC1215 I-BRD9 Bromosporine PLX51107 GSK1324726A (I-BET726) Pelabresib (CPI-0610) PF-CBP1 HCl INCB054329 MS436 GSK2801 UNC669 MZ-1 NEO2734 OF-1 CPI-637 GSK6853 I-CBP112 BI-7273 PFI-4 INCB057643 GSK 5959 dBET57 BI-9564 Histone Acetyltransferase Inhibitor II	点击展开
相关化合物库	激酶抑制剂库 FDA药物库天然产物库已知活性药物库-I 高选择性抑制剂库	点击展开

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

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]
激酶实验	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
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

参考文献
[1] Noel JK, et al. Mol Cancer Ther. 2013, 12, C244. [2] Boi M, et al. Mol Cancer Ther. 2013, 12, A219.

参考文献