Voxtalisib (XL765)

製品コードS7646 バッチS764602

印刷

化学情報

Synonyms

SAR245409

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₃H₁₄N₆O

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

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	1.450mg/ml (5.36mM)	Taking the 1 mL working solution as an example, add 50 μL of 29 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.180mg/ml (0.67mM)	Taking the 1 mL working solution as an example, add 50 μL of 3.6 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	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.
in vitro	Voxtalisib (XL765) is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). It also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. ^[1] This compound, 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. Treatment with it results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. The effect can be recapitulated by using combinations of single-targeted compounds. It 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	Voxtalisib (XL765) in combination with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while this compound alone at the same dose (30 mg/kg) has no inhibitory effect. ^[2] Its oral administration 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. When combined with temozolomide (TMZ), it 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.)
	濃度	Dissolved in DMSO, final concentration ~10 μM
	反応時間	24, 48, 72 hours
	実験の流れ	Twenty-four hours after plating, cells are treated with Voxtalisib (XL765) and harvested for apoptosis or autophagy assays at 24, 48, or 72 hours after treatment with this compound. 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 treated versus control cells.
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

https://pubmed.ncbi.nlm.nih.gov/18794885/
https://pubmed.ncbi.nlm.nih.gov/21678117/
https://pubmed.ncbi.nlm.nih.gov/21317208/

カスタマーフィードバック

: Data from [Data independently produced by , , Biomed Pharmacother, 2018, 103:1069-1078]

: 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
Overexpression of Long Noncoding RNA H19 Downregulates miR-140-5p and Activates PI3K/AKT Signaling Pathway to Promote Invasion, Migration and Epithelial-Mesenchymal Transition of Ovarian Cancer Cells [ Biomed Res Int, 2021, 2021:6619730]	PubMed: 34250088
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

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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