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受注：045-509-1970 |
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化学情報
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Synonyms | SAR245409 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C13H14N6O |
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| 分子量 | 270.29 | CAS No. | 934493-76-2 | |
| Solubility (25°C)* | 体外 | DMSO | 29 mg/mL (107.29 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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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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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Voxtalisib (SAR245409, XL765) is a dual inhibitor of mTOR/PI3K, mostly for p110γ with IC50 of 9 nM; also inhibits DNA-PK and mTOR. Phase 1/2. |
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| in vitro | XL765 is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). XL765 also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. [1] XL765 treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. XL765, a dual-target PI3K/mTOR inhibitor, inhibits cell growth and apoptosis in many more cell lines and at lower concentrations as compared to the PI3K-selective inhibitors XL147 and PIK90. The effect can be recapitulated by using combinations of single-targeted compounds. XL765 significantly reduces phosphorylation of the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K inhibition alone. XL765 treatment causes accumulation of autophagosomes in MIAPaCa-2 cells, and results in significant dose-dependent AVO induction and LC3-II stimulation in MIAPaCa-2 cells stably expressing a LC3-GFP construct. [2] |
| in vivo | The combination of XL765 (30 mg/kg) with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while XL765 alone at the same dose has no inhibitory effect. [2] Oral administration of XL765 results in greater than 12-fold reduction in median tumor bioluminescence compared to control and improvement in median survival in nude mice implanted intracranially with GBM 39-luc cells. XL765 in combination with temozolomide (TMZ) yields a 140-fold reduction in median bioluminescence with a trend toward improvement in median survival compared with TMZ alone. [3] |
プロトコル(参考用のみ)
| 細胞アッセイ | 細胞株 | Pancreatic cancer cell lines (HcG25, Panc89, PA-TU8988T, Panc2.13, MiaPaCa2, Panc10.05, Panc8.13, BxPC-3, etc.) |
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| 濃度 | Dissolved in DMSO, final concentration ~10 μM | |
| 反応時間 | 24, 48, 72 hours | |
| 実験の流れ | Cells are treated with XL765 24 hours after plating and harvested for apoptosis or autophagy assays at 24, 48, or 72 hours after XL765 treatment. Apoptosis is determined by total percentage of annexin V-positive cells by fluorescence-activated cell sorting (FACS). Acidic vesicular organelles (AVOs) are detected in XL765-treated cells by vital staining with acridine orange. The degree of AVO formation is expressed as fold increase of acridine orange fluorescence intensity (FL3) in XL765-treated cells versus control cells. |
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| 動物実験 | 動物モデル | Female Nu/Nu mice inoculated s.c. with BxPC-3 cells |
| 投薬量 | 30 mg/kg | |
| 投与方法 | Oral gavage once a day |
参考
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カスタマーフィードバック
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Data from [Data independently produced by , , Biomed Pharmacother, 2018, 103:1069-1078]
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Data from [Data independently produced by , , Int J Oncol, 2015, 47(3):1143-59. ]
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：
| Kinase inhibitor-induced cardiotoxicity assessed in vitro with human pluripotent stem cell derived cardiomyocytes [ Toxicol Appl Pharmacol, 2022, 437:115886] | PubMed: 35041852 |
| Identification of a DNA Methylation-Driven Genes-Based Prognostic Model and Drug Targets in Breast Cancer: In silico Screening of Therapeutic Compounds and in vitro Characterization [ Front Immunol, 2021, 12:761326] | PubMed: 34745136 |
| Comprehensive pharmacogenomic characterization of gastric cancer. [ Genome Med, 2020, 18;12(1):17] | PubMed: 32070411 |
| The PI3K/mTOR dual inhibitor GSK458 potently impedes ovarian cancer tumorigenesis and metastasis. [ Cell Oncol (Dordr), 2020, 8] | PubMed: 32382996 |
| Birinapant Enhances Gemcitabine's Anti-tumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis [ Mol Cancer Ther, 2020, molcanther.1160.2019] | PubMed: 33323457 |
| PI3K/mTOR inhibition of IDH1 mutant glioma leads to reduced 2HG production that is associated with increased survival. [ Sci Rep, 2019, 9(1):10521] | PubMed: 31324855 |
| In vitro anti-leukemia activity of dual PI3K/mTOR inhibitor Voxtalisib on HL60 and K562 cells, as well as their multidrug resistance counterparts HL60/ADR and K562/A02 cells [Zhang L, et al. Biomed Pharmacother, 2018, 103:1069-1078] | PubMed: 29710665 |
| Primary resistance to EGFR inhibition in glioblastoma is mediated by a TNF-JNK-Axl-ERK signaling axis [Guo G, et al. Nat Neurosci, 2017, 20(8):1074-1084] | PubMed: 28604685 |
| Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma. [ Cancer Cell, 2016, 29(4):563-573] | PubMed: 27070703 |
| Glucose-dependent acetylation of Rictor promotes targeted cancer therapy resistance [ Proc Natl Acad Sci U S A, 2015, 112(30):9406-11] | PubMed: 26170313 |
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。