Birabresib (OTX015)

製品コードS7360 バッチS736008

印刷

化学情報

Chemical Structure Synonyms MK 8628 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H22ClN5O2S
分子量 491.99 CAS No. 202590-98-5
Solubility (25°C)* 体外 DMSO 98 mg/mL (199.19 mM)
Ethanol 98 mg/mL (199.19 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

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.
in vitro Birabresib (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] It results in rapid down-regulation of c-MYC expression, and shows synergistic anti-proliferative effects in combination with ALK inhibitors in ALKpos ALCL cell lines. [2]
in vivo Birabresib (OTX015) 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, when administered p.o. [1]
特徴 Orally bioavailable BRD2/3/4-selective inhibitor that has been tested in Phase I clinical trials for treatment of Haematological Malignancies.

プロトコル(参考用のみ)

キナーゼアッセイ TR-FRET Assay [1]
To assess binding of Birabresib (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 this compound 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.
細胞アッセイ 細胞株 Human tumor cells
濃度 ~2 μM
反応時間 72 hours
実験の流れ

Effects of Birabresib (OTX015) on cancer cell proliferation are evaluated by incubating human tumor cells for 72 h with increasing concentrations of this compound and assessing proliferation using a tetrazolium salt (WST-8)-based colorimetric assay.
動物実験 動物モデル BLAB/c-nu/nu mice bearing established Ty82 BRD-NUT midline carcinoma xenografts.
投薬量 ~100 mg/kg
投与方法 p.o.

参考

  • http://mct.aacrjournals.org/content/12/11_Supplement/C244.short
  • http://mct.aacrjournals.org/content/12/11_Supplement/A219.short

カスタマーフィードバック

, , Mol Cancer Ther, 2016, 16(4 suppl 1):S263-S276

Data from [Data independently produced by , , Clin Cancer Res, 2018, 24(16):3941-3954]

Data from [Data independently produced by , , Clin Cancer Res, 2018, doi: 10.1158/1078-0432.CCR-18-1040]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Dual targeting of CDK6 and LSD1 is synergistic and overcomes differentiation blockade in AML [ EMBO Mol Med, 2025, 10.1038/s44321-025-00296-2] PubMed: 40883610
Dual Inhibition of CDK4/6 and XPO1 Induces Senescence With Acquired Vulnerability to CRBN-Based PROTAC Drugs [ Gastroenterology, 2024, S0016-5085(24)00062-3] PubMed: 38262581
Targeting of mutant-p53 and MYC as a novel strategy to inhibit oncogenic SPAG5 activity in triple negative breast cancer [ Cell Death Dis, 2024, 15(8):603] PubMed: 39164278
RAPID resistance to BET inhibitors is mediated by FGFR1 in glioblastoma [ Sci Rep, 2024, 14(1):9284] PubMed: 38654040
HNF4α, SP1 and c-myc are master regulators of CNS autoimmunity [ J Autoimmun, 2023, 138:103053] PubMed: 37236124
"Proteotranscriptomic analysis of advanced colorectal cancer patient derived organoids for drug sensitivity prediction" [ J Exp Clin Cancer Res, 2023, 42(1):8] PubMed: 36604765
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Combination drug screen targeting glioblastoma core vulnerabilities reveals pharmacological synergisms [ EBioMedicine, 2023, 95:104752] PubMed: 37572644
Pharmacological inhibition of bromodomain and extra-terminal proteins induces an NRF-2-mediated antiviral state that is subverted by SARS-CoV-2 infection [ PLoS Pathog, 2023, 19(9):e1011657] PubMed: 37747932
ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD [ Mol Oncol, 2023, 17(7):1402-1418] PubMed: 36567628

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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