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受注：045-509-1970 |
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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C47H55ClF3N5O6S3 |
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| 分子量 | 974.61 | CAS No. | 923564-51-6 | |
| Solubility (25°C)* | 体外 | |||
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* <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. |
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生物活性
| 製品説明 | ナビトクラックス (Navitoclax (ABT-263)) は Bcl-xL, Bcl-2 and Bcl-w の強力な阻害剤であり、阻害定数は cell-free assay において Ki ≦ 0.5 nM, 1 nM および 1nM です。一方、Mcl-1 および A1 に対しては比較的弱い結合力を示します。臨床第2相試験中 |
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| in vitro | ABT-263 is structurally related to ABT-737; it is a disruptor of Bcl-2/Bcl-xL interactions with pro-apoptotic proteins. Overexpression of the prosurvival Bcl-2 family members is commonly associated with tumor maintenance, progression, and chemoresistance. [1] ABT-263 displays the protection afforded by overexpression of Bcl-2 or Bcl-xL with EC50 values of 60 nM and 20 nM, respectively. [1] A wide range of cellular activity is observed with ABT-263 having a 50% growth inhibition (EC50) of 110 nM against the most sensitive line (H146), whereas its activity in the least sensitive line (H82) results in an EC50 at 22 μM. All four cell lines with EC50 values of <400 nM (H146, H889, H1963, and H1417) are also highly sensitive to ABT-737, and the two most resistant lines (H1048 and H82) are similarly resistant to ABT-263. [2] |
| in vivo | When ABT-263 is administered at 100 mg/kg/day in the H345 xenograft model, significant antitumor efficacy is observed with 80% TGI and 20% of treated tumors indicating at least a 50% reduction in tumor volume. [2] Oral administration of ABT-263 alone causes complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 displays modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. [2] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Affinity determination | |
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| Binding affinities (Ki or IC50) of ABT-263 against different isoforms of Bcl-2 family are determined with competitive fluorescence polarization assays. The following peptide probe/protein pairs are used: f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM), f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM), and f-Bax (1 nM) and Bcl-2-A1 (15 nM). Binding affinities for Bcl-xL are also determined using a time-resolved fluorescence resonance energy transfer assay. Bcl-xL (1 nM, His tagged) is mixed with 200 nM f-Bak, 1 nM Tb-labeled anti-His antibody, and ABT-263 at room temperature for 30 min. Fluorescence is measured on an Envision plate reader using a 340/35 nm excitation filter and 520/525 (f-Bak) and 495/510 nm (Tb-labeled anti-His antibody) emission filters. | ||
| 細胞アッセイ | 細胞株 | SCLC cell lines |
| 濃度 | 0-1 μM | |
| 反応時間 | 48 hours | |
| 実験の流れ | Human tumor cell lines SCLC cell lines are maintained at 37℃ containing 5% CO2. SCLC cell lines are cultured in RPMI 1640 with 10% fetal bovine serum (FBS), 1% sodium pyruvate, 25 mM HEPES, 4.5 g/L glucose, and 1% penicillin/streptomycin. Leukemia and lymphoma cell lines are cultured in RPMI 1640 supplemented with 10% FBS and 1% penicillin/streptomycin. Cells (1-5×10 4) are treated by ABT-263 for 48 hours in 96-well culture plates in a final volume of 100 μL and cytotoxicity is assessed with the CellTiter Glo assay. In vitro cyto toxicity of ABT-263 is assayed. |
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| 動物実験 | 動物モデル | C.B.-17 scid-bg or C.B.-17 scid mice |
| 投薬量 | 100 mg/kg/d | |
| 投与方法 | Administered via p.o. | |
参考
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カスタマーフィードバック
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Data from [PLoS One, 2011, 6, e21980]
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Data from [PLoS One, 2011, 6, e21980]
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Data from [PLoS One, 2011, 6, e21980]
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 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 |
| Detection of senescence using machine learning algorithms based on nuclear features [ Nat Commun, 2024, 15(1):1041] | PubMed: 38310113 |
| Targeting of vulnerabilities of drug-tolerant persisters identified through functional genetics delays tumor relapse [ Cell Rep Med, 2024, 5(3):101471] | PubMed: 38508142 |
| Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment [ Theranostics, 2024, 14(3):1224-1240] | PubMed: 38323313 |
| Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells [ Redox Biol, 2024, 76:103323] | PubMed: 39180983 |
| Bi-directional neuro-immune dysfunction after chronic experimental brain injury [ J Neuroinflammation, 2024, 21(1):83] | PubMed: 38581043 |
| Bi-directional neuro-immune dysfunction after chronic experimental brain injury [ J Neuroinflammation, 2024, 21(1):83] | PubMed: 38581043 |
| Combined inhibition of class 1-PI3K-alpha and delta isoforms causes senolysis by inducing p21WAF1/CIP1 proteasomal degradation in senescent cells [ Cell Death Dis, 2024, 15(5):373] | PubMed: 38811535 |
| Recruitment of BAG2 to DNAJ-PKAc scaffolds promotes cell survival and resistance to drug-induced apoptosis in fibrolamellar carcinoma [ Cell Rep, 2024, 43(2):113678.] | PubMed: 38236773 |
| Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality [ JCI insight, 2024, 9(2):e173863.] | PubMed: none |
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。