Birabresib (OTX015)

Birabresib (OTX015, MK 8628) is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Birabresib inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.

CAS No. 202590-98-5

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 41800	国内在庫あり
2mg	JPY 22000	国内在庫あり
10mg	JPY 67000	国内在庫あり
1g	JPY 595500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

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製品安全説明書

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Birabresib (OTX015)関連製品

関連ターゲット	BET p300/CBP BRPF bromodomain	もっと見る
関連製品	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	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Bioactive Compound Library-Ⅱ	もっと見る

シグナル伝達経路

Epigenetic Reader Domainシグナル伝達経路

Epigenetic Reader Domain阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
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
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

生物活性

製品説明

Birabresib (OTX015, MK 8628) is a potent BET bromodomain inhibitor with EC50 ranging from 10 to 19 nM for BRD2, BRD3, and BRD4 in cell-free assays. Birabresib inhibits the expression of Nuclear receptor binding SET domain protein 3 (NSD3) target genes.

特性

Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.

Targets

BRDs ^[1]
(Cell-free assay)

10-19 nM(EC50)

In Vitro
In vitro	OTX015 inhibits the binding of BRD2, BRD3, and BRD4 to AcH4 with IC50 ranging from 92 to 112 nM, and inhibits the growth of a variety of human cancer cell lines with GI50 ranging from 60 to 200 nM. ^[1] OTX015 results in rapid down-regulation of c-MYC expression, and show the synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines. ^[2]
Kinase Assay	TR-FRET Assay ^[1]
Kinase Assay	To assess binding of OTX015 to BRD2, BRD3, and BRD4, BRD-expressing CHO cell lysate (from CHO cells transfected with expression plasmids for Flag-tagged BRD2, BRD3, or BRD4 or vector alone), europium-conjugated anti-Flag antibody, XL-665-conjugated streptavidin, and biotinylated OTX015 are incubated at room temperature for 0.2 to 2 h. Fluorescence is measured by TR-FRET using an EnVision 2103 Multilabel Reader and EC50 for binding is calculated by nonlinear regression using PRISM version 5.02.
細胞実験	細胞株	Human tumor cells
	濃度	~2 μM
	反応時間	72 hours
	実験の流れ	Effects of OTX015 on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of OTX015 and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	ZO-1 / Vimentin JAK2 / p-STAT5 / STAT5 / p-STAT3 / c-Myc / PIM1 / CDK6 / HEXIM1 / p27 / p21 / Bcl-xL / γH2AX c-Myc BRD4		27980063
	Immunofluorescence	Vimentin BRD4		27980063

In Vivo
In Vivo	OTX015 (p.o.) significantly inhibits the growth of Ty82 BRD-NUT midline carcinoma tumors in nude mice by 79% at 100 mg/kg qd and 61% at 10 mg/kg bid, respectively. ^[1]
動物実験	動物モデル	BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts.
	投与量	~100 mg/kg
	投与経路	p.o.

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試験 (data from https://clinicaltrials.gov, updated on 2024-01-11)
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
[1] Noel JK, et al. Mol Cancer Ther. 2013, 12, C244. [2] Boi M, et al. Mol Cancer Ther. 2013, 12, A219.

参考

化学情報

分子量	491.99	化学式	C₂₅H₂₂ClN₅O₂S
CAS No.	202590-98-5	SDF	Download Birabresib (OTX015) SDFをダウンロードする
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
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 98 mg/mL ( (199.19 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 98 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):