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Voxtalisib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Voxtalisib图片
CAS NO:934493-76-2
包装与价格:
包装价格(元)
Free Sample (0.1-0.5mg)电议
10mM (in 1mL DMSO)电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品介绍
Voxtalisib (XL-765) 是一种有效的 PI3K 抑制剂,抑制p110α,p110β,p110γ 和 p110δ,IC50 分别为 39, 113, 9 和 43 nM,也抑制 DNA-PK (IC50=150 nM) 和 mTOR (IC50=157 nM)。Voxtalisib (XL-765) 抑制 mTORC1 和 mTORC2,IC50s 分别为 160 和 910 nM。
Cas No.934493-76-2
别名XL765; SAR245409
Canonical SMILESO=C1C(C2=NNC=C2)=CC3=C(C)N=C(N)N=C3N1CC
分子式C13H14N6O
分子量270.29
溶解度DMSO: 10 mg/mL (37.00 mM)
储存条件Store at -20°C
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

Voxtalisib (XL-765) is a potent PI3K inhibitor, which has a similar activity toward class I PI3K (IC50s=39, 113, 9 and 43 nM for p110α, p110β, p110γ and p110δ, respectively), also inhibits DNA-PK (IC50=150 nM) and mTOR (IC50=157 nM). Voxtalisib (XL-765) inhibits mTORC1 and mTORC2 with IC50s of 160 and 910 nM, respectively. p110γ|9 nM (IC50)|p110α|39 nM (IC50)|p110δ|43 nM (IC50)|p110β|113 nM (IC50)|mTOR|157 nM (IC50)|mTORC1|160 nM (IC50)|mTORC2|910 nM (IC50)|DNA-PK|150 nM (IC50)

Voxtalisib (XL-765) displays potent inhibitory activity against class I PI3K isoforms p110α, p110β, p110δ, and p120γ, with IC50s of 39, 110, 43, and 9 nM, respectively. The IC50 value for inhibition of PI3Kα by Voxtalisib (XL-765) is determined at various concentrations of ATP, revealing Voxtalisib (XL-765) be an ATP-competitive inhibitor with an equilibrium inhibition constant (Ki) value of 13 nM. Voxtalisib (XL-765) also inhibits mTOR (IC50s of 160 and 910 nM for mTORC1 and mTORC2, respectively) in an immune-complex kinase assay and the PI3K-related kinase DNA-PK (IC50 value of 150 nM). In contrast, Voxtalisib (XL-765) has relatively weak inhibitory activity toward the class III PI3K vacuolar sorting protein 34 (VPS34; IC50 value of ~9.1 μM). Consistent with its inhibitory activity against purified PI3K proteins, SAR245409 inhibits EGF-induced PIP3 production in PC-3 and MCF7 cells with IC50s of 290 and 170 nM, respectively. The ability of Voxtalisib (XL-765) to inhibit phosphorylation of key signaling proteins downstream of PI3K is examined by assessing its effects on EGF-stimulated phosphorylation of AKT and on nonstimulated phosphorylation of S6 in PC-3 cells by cell-based ELISA. Voxtalisib (XL-765) inhibits these activities with IC50s of 250 and 120 nM, respectively. In MCF7 and PC-3 cells, Voxtalisib (XL-765) inhibits proliferation (monitored by BrdUrd incorporation) with IC50s of 1,070 and 1,840 nM, respectively. To further characterize the effects of Voxtalisib (XL-765) on tumor cell growth, an assay monitoring the anchorage-independent growth of PC-3 and MCF7 cells in soft agar over a 14-day period is used. SAR245409 inhibits colony growth with an IC50 value of 270 nM in PC-3 cells and 230 nM in MCF7 cells[2].

Oral administration of Voxtalisib (XL-765) causes a dose-dependent decrease of phosphorylation of AKT, p70S6K, and S6 in the tumors, reaching a maximum of 84% inhibition of S6 phosphorylation at 30 mg/kg at 4 hours. The dose-response relationships derive from the 4 hours time point predict 50% inhibition of AKT, p70S6K, and S6 phosphorylation to occur at doses of 19 mg/kg (pAKTT308 and pAKTS473), 51 mg/kg (p-p70S6K), and 18 mg/kg (pS6). Inhibition of AKT, p70S6K, and S6 phosphorylation in MCF7 tumors following a 30 mg/kg dose of Voxtalisib (XL-765) is maximal at 4 hours, reaching 61% to 84%; however, the level of inhibition decreases to 0% to 42% by 24 hours, and minimal or no inhibition is evident by 48 hours. Following a 100 mg/kg dose of Voxtalisib (XL-765), inhibition is also maximal at 4 hours (52%-75%)[2].

[1]. Garcia-Echeverria C, et al. Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene. 2008 Sep 18;27(41):5511-26. [2]. Yu P, et al. Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations affecting the PI3K pathway. Mol Cancer Ther. 2014 May;13(5):1078-91.