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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.
CAS No. 202590-98-5
文献中Selleckの製品使用例（69）
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純度：
99.9%
99.9
Birabresib (OTX015)関連製品
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 |
| 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 |
|
| 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. |
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| 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 |
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 |
実験計算
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
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。
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