| 名称 | Voxtalisib |
| 描述 | Voxtalisib (XL765) (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. |
| 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 | Voxtalisib is active against class I PI3K (IC50 = 39, 113, 9 and 43 nM for p110α, β, γ and δ, respectively). Voxtalisib also inhibits DNA-PK (IC50 = 150 nM) and mTOR (IC50 = 157 nM) but not XL-147 which shows IC50 values of > 15 μM. [1] Voxtalisib treatment results in decreased cell viability in 13 PDA cell lines in a dose-dependent manner. Voxtalisib, 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. Voxtalisib significantly reduces phosphorylation of the mTOR targets S6, S6K, and 4EBP1, which is associated with greater apoptosis induction rather than to PI3K inhibition alone. Voxtalisib 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 Voxtalisib (30 mg/kg) with chloroquine (50 mg/kg) results in significant inhibition of BxPC-3 xenograft growth in mice models, while Voxtalisib alone at the same dose has no inhibitory effect. [2] Oral administration of Voxtalisib 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. Voxtalisib 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 | Shipping with blue ice. |
| 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)
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| 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 | L-Leucine | Capivasertib | Myricetin | Erucic acid | Sapanisertib | (2S,3R,4S)-4-Hydroxyisoleucine | Duvelisib (R enantiomer) hydrochloride | Isoprenaline hydrochloride | Quercetin | Quercetin Dihydrate | Rapamycin | Apilimod |
| 相关库 | 经典已知活性库 | ReFRAME 相关化合物库 | 激酶抑制剂库 | 抗癌临床化合物库 | 药物功能重定位化合物库 | 抑制剂库 | 抗衰老化合物库 | 已知活性化合物库 | 抗癌活性化合物库 | 抗癌药物库 |
United States
