Product Introduction
Bioactivity


英文名: Voxtalisib

描述: Voxtalisib (XL765) 是一种PI3K 抑制剂，抑制p110α，p110β，p110γ和p110δ。它抑制mTORC1和mTORC2，IC50s 分别为 160 和 910 nM。它也抑制 DNA-PK (其 IC50=150 nM) 和 mTOR (其 IC50=157 nM)。

细胞实验: 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. (Only for Reference)

体外活性: 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]

体内活性: 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]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 50 mg/mL (185 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: SAR-245409 | inhibit | Phosphoinositide 3-kinase | Mammalian target of Rapamycin | XL-765 | mTOR | PI3K | Inhibitor | SAR 245409 | Voxtalisib | XL 765

相关产品: PIK-75 | OSI-027 | KU-57788 | DMNB | NU6027 | PIK-90 | IC 86621 | KU-55933 | BAY-8400 | Torin 1

相关库: Drug Repurposing Compound Library | PI3K-AKT-mTOR Compound Library | Anti-Cancer Drug Library | Inhibitor Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Anti-Cancer Active Compound Library | Metabolism Compound Library | Reprogramming Compound Library | Bioactive Compound Library