Sabutoclax

製品コードS8061 バッチS806103

印刷

化学情報

Chemical Structure Synonyms BI-97C1 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C42H40N2O8
分子量 700.78 CAS No. 1228108-65-3
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 100 mg/mL (142.69 mM)
Ethanol (warmed with 50ºC water bath) 25 mg/mL (35.67 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
5.0mg/ml Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
5% DMSO 95% corn oil
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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 Sabutoclax (BI-97C1) is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.
in vitro BI-97C1 potently inhibits cell growth of human prostate cancer, lung cancer, and lymphoma cell lines with EC50 values of 0.13, 0.56, and 0.049 μM, respectively, and shows little cytotoxicity against bax-/-bak-/- cells[1]. It is suggest that treatment with the combination regimen of mda-7/IL-24 and BI-97C1 induces autophagy that facilitates apoptosis in association with up-regulation of NOXA, accumulation of Bim, and activation of Bax and Bak[2].
in vivo BI-97C1 displays in vivo efficacy in transgenic mice in which Bcl-2 is overexpressed in splenic B-cells and also demonstrates superior single-agent antitumor efficacy in a prostate cancer mouse xenograft model that depends on Mcl-1 for survival[1]. Treatment with Ad.5/3-mda-7 and BI-97C1 significantly inhibits the growth of human PC xenografts in nude mice and spontaneously induced PC in Hi-myc transgenic mice. Tumor growth inhibition correlats with increased TUNEL staining and decreased Ki-67 expression in both PC xenografts and prostates of Hi-myc mice[2].

プロトコル(参考用のみ)

キナーゼアッセイ Competitive fluorescence polarization assays (FPA)
A Bak BH3 peptide (F-BakBH3) (GQVGRQLAIIGDDINR) is labeled at the N-terminus with fluorescein isothiocyanate (FITC) and purified by HPLC. For competitive binding assays, 100 nM GST-Bcl-XL ΔTM protein is preincubated with the tested compound at varying concentrations in 47.5 μL PBS (pH = 7.4) in 96-well black plates at room temperature for 10 min, and then 2.5 μL of 100 nM FITC-labeled Bak BH3 peptide is added to produce a final volume of 50 μL. The wild-type and mutant Bak BH3 peptides are included in each assay plate as positive and negative controls, respectively. After 30 min incubation at room temperature, the polarization values in millipolarization units are measured at excitation/emission wavelengths of 480/535 nm with a multilabel plate reader. IC50 is determined by fitting the experimental data to a sigmoidal dose-response nonlinear regression model. Data reported are mean of three independent experiments. Performance of Bcl-2 and Mcl-1FPA are similar. Briefly, 50 nM of GST-Bcl-2 or -Mcl-1are incubatedwith various concentrations of compound (4 and 11-14) for 2 min, and then 15 nM FITC-conjugated-Bim BH3 peptide is added in PBS buffer. Fluorescence polarization is measured after 10 min.
細胞アッセイ 細胞株 PC3, H460, H1299
濃度 ~1 μM
反応時間 72 h
実験の流れ ATP-LITE assay
動物実験 動物モデル Bcl-2 transgenic mice, human prostate cancer xenografts
投薬量 1 mg/kg, 3 mg/kg, 5 mg/kg
投与方法 intraperitoneally

カスタマーフィードバック

Data from [Data independently produced by , , Cell Death Differ, 2016, 23(10):1681-90.]

Data from [Data independently produced by , , Cancer Lett, 2018, 423:47-59]

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：

Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 12(18)2247] PubMed: 37759469
Obatoclax Rescues FUS-ALS Phenotypes in iPSC-Derived Neurons by Inducing Autophagy [ Cells, 2023, 10.3390/cells12182247] PubMed: 37759469
Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1 [ Mol Divers, 2022, 10.1007/s11030-022-10494-6] PubMed: 35909144
Comparison of putative BH3 mimetics AT-101, HA14-1, sabutoclax and TW-37 with ABT-737 in platelets. [ Platelets, 2020, 10.1080/09537104.2020.1724276] PubMed: 32079453
Alveolar Macrophage Apoptosis-associated Bacterial Killing Helps Prevent Murine Pneumonia. [ Am J Respir Crit Care Med, 2019, 200(1):84-97] PubMed: 30649895
Targeting CDK6 and BCL2 Exploits the "MYB Addiction" of Ph+ Acute Lymphoblastic Leukemia [De Dominici M, et al. Cancer Res, 2018, 78(4):1097-1109] PubMed: 29233926
Sabutoclax, pan-active BCL-2 protein family antagonist, overcomes drug resistance and eliminates cancer stem cells in breast cancer [Hu Y, et al. Cancer Lett, 2018, 423:47-59] PubMed: 29496539
PPARγ is critical forMycobacterium tuberculosisinduction of Mcl-1 and limitation of human macrophage apoptosis [ PLoS pathogens, 2018, 14(6): e1007100.] PubMed: None
PPARγ is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis. [ PLoS Pathog, 2018, 14(6):e1007100] PubMed: 29928066
PTBP1 modulation of MCL1 expression regulates cellular apoptosis induced by antitubulin chemotherapeutics [Cui J, et al. Cell Death Differ, 2016, 23(10):1681-90] PubMed: 27367564

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。