Obatoclax Mesylate (GX15-070)

製品コードS1057 バッチS105703

印刷

化学情報

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

C20H19N3O.CH4O3S
分子量 413.49 CAS No. 803712-79-0
Solubility (25°C)* 体外 DMSO 83 mg/mL (200.73 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol
30.0mg/ml Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. 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 Obatoclax Mesylate (GX15-070) is an antagonist of Bcl-2 with Ki of 0.22 μM in a cell-free assay, can assist in overcoming MCL-1 mediated resistance to apoptosis.
in vitro

Obatoclax completely inhibits Bak recovery of Mcl-1 at 5 μM in SK-Mel5 cells and overcomes resistance to ABT-373-induced apoptosis conferred by Mcl-1 in KB/Bcl-2 cells. [1] Obatoclax is a BH3 mimetic which binds to a broad spectrum of Bcl-2 family members, including Bcl-2, Bcl-xL, and Mcl-1. Obatoclax uniquely displaces BH3 domains by activation of the pocket of Mcl-1 followed by a triggering of apoptosis mediated by oligomerization of Bak and release of cytochrome c. Obatoclax is sensitive to Bcl-xL in cell lines lacking it or showing low expression. It shows low cytotoxicity to Mcl-1, Bcl-2, and Bcl-xL in all the strongly-expressed cell lines. Obatoclax inhibits multiple myeloma (MM) cell lines (KMS12PE, KMS18, MY5, etc.) with IC50 values ranging from 52 to 1100 nM and the inhibition is umimpaired even in the presence of IL-6 or IGF-1, which are resistance to cytotoxic agents, at a concentration of 150 nM. Obatoclax enhances the antimyeloma activity induced by melphalan, dexamethasone, or bortezomib. [2] Obatoclax potentiates TRAIL (tumor necrosis factor-related apoptosis-inducing ligand)-mediated apoptosis by unsequestering Bak and Bim from Bcl-2/Bcl-xL or Mcl-1 proteins in PANC-1 and BxPC-3 cells. [3]
in vivo

Obatoclax also exhibits high antitumor activity in SCID mice bearing human C33A cerivical carcinoma tumors at a dose of 0.5 mg/kg. [1]
特徴 Potential 1st-in-class small molecule antagonist of Bcl-2 designed to inhibit all relevant Bcl-2 family members, including Mcl-1.

プロトコル(参考用のみ)

キナーゼアッセイ Bcl-2 Binding affinity calculation
A predicted binding affinity for Obatoclax binding to BCL-2 is calculated using the SIE scoring function. [4] As a control in determining the reliability of the calculation, predicted binding affinities Ki) are calculated for a set of 12 small molecules with experimentally measured binding affinities to BCL-2.
細胞アッセイ 細胞株 Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs)
濃度 ~10 μM
反応時間 48-72 hours
実験の流れ

Obatoclax is dissolved in DMSO at a stock concentration of 5 mM. Cell viability is assayed by MTT. Human MM cells (HMCLs), peripheral blood lymphocytes (PBLs), bone marrow stromal cells (BMSCs) are seeded in 96-well plates at a density of 2 × 104 per well for HMCLs or 5~10 × 103 for PBLs. Various concentrations of Obatoclax are added to the cells, with or without IGF-1 (50 ng/mL) or IL-6 (10 ng/mL). Cells are incubated for 48-72 hours and cell viability is determined.
動物実験 動物モデル Female BALB/c or CB17 SCID/SCID mice bearing SW480, C33A, PC3, and 4T1 cells are used.
投薬量 0.0313, 0.25, 0.5 and 2 mg/kg
投与方法 Administered intravenously (tail vein) once a day

カスタマーフィードバック

Data from [Data independently produced by Cancer Lett, 2014, 348, 20-8]

Data from [Data independently produced by Exp Cell Res, 2014, 322, 217-25]

Data from [Data independently produced by Cell Death Dis, 2012, 19, 3:e351]

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：

Gravitational and mechanical forces drive mitochondrial translation [ bioRxiv, 2024, 10.1101/2023.01.18.524628] PubMed: none
Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro [ Emerg Microbes Infect, 2022, 1-29] PubMed: 34989664
Trabectedin Is Active against Two Novel, Patient-Derived Solitary Fibrous Pleural Tumor Cell Lines and Synergizes with Ponatinib [ Cancers (Basel), 2022, 14(22)5602] PubMed: 36428694
Computational analysis of cholangiocarcinoma phosphoproteomes identifies patient-specific drug targets [ Cancer Res, 2021, canres.0955.2021] PubMed: 34551960
Inhibition of the Anti-Apoptotic Bcl-2 Family by BH3 Mimetics Sensitize the Mitochondrial Permeability Transition Pore Through Bax and Bak [ Front Cell Dev Biol, 2021, 9:765973] PubMed: 34926454
Obatoclax, the pan-Bcl-2 inhibitor sensitizes hepatocellular carcinoma cells to promote the anti-tumor efficacy in combination with immune checkpoint blockade [ Transl Oncol, 2021, 14(8):101116] PubMed: 33975180
Dual-stimuli responsive nanotheranostics for mild hyperthermia enhanced inhibition of Wnt/β-catenin signaling. [ Biomaterials, 2020, 232:119709] PubMed: 31896513
Development and implementation of the SUM breast cancer cell line functional genomics knowledge base [ NPJ Breast Cancer, 2020, 6:30] PubMed: 32715085
Obatoclax, a Pan-BCL-2 Inhibitor, Downregulates Survivin to Induce Apoptosis in Human Colorectal Carcinoma Cells Via Suppressing WNT/β-catenin Signaling. [ Int J Mol Sci, 2020, 5;21(5) pii: E1773] PubMed: 32150830
The pan-Bcl-2 inhibitor obatoclax promotes differentiation and apoptosis of acute myeloid leukemia cells. [ Invest New Drugs, 2020, 4] PubMed: 32367199

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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