Birabresib (OTX015)

別名:MK 8628

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.

Birabresib (OTX015)化学構造

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
JPY 22000 国内在庫あり
JPY 67000 国内在庫あり
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]
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製品安全説明書

現在のバッチを見る: 純度: 99.9%
99.9

Birabresib (OTX015)関連製品

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
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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]
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
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

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

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)

mg/kg g μL

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。

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