Voxtalisib (XL765) is a potentPI3Kinhibitor, which has a similar activity toward class IPI3K(IC₅₀s=39, 113, 9 and 43 nM forp110α,p110β,p110γandp110δ, respectively), also inhibitsDNA-PK(IC₅₀=150 nM) andmTOR(IC₅₀=157 nM). Voxtalisib (XL765) inhibitsmTORC1andmTORC2withIC₅₀s of 160 and 910 nM, respectively.

Voxtalisib (XL765) 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 IC₅₀value for inhibition of PI3Kα by Voxtalisib is determined at various concentrations of ATP, revealing Voxtalisib be an ATP-competitive inhibitor with an equilibrium inhibition constant (K_i) value of 13 nM. Voxtalisib 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 (IC₅₀value of 150 nM). In contrast, Voxtalisib (XL765) has relatively weak inhibitory activity toward the class III PI3K vacuolar sorting protein 34 (VPS34; IC₅₀value of ~9.1 μM). Consistent with its inhibitory activity against purified PI3K proteins, SAR245409 inhibits EGF-induced PIP₃production in PC-3 and MCF7 cells with IC₅₀s of 290 and 170 nM, respectively. The ability of Voxtalisib 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 inhibits these activities with IC₅₀s of 250 and 120 nM, respectively. In MCF7 and PC-3 cells, Voxtalisib inhibits proliferation (monitored by BrdUrd incorporation) with IC₅₀s of 1,070 and 1,840 nM, respectively. To further characterize the effects of Voxtalisib 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 IC₅₀value of 270 nM in PC-3 cells and 230 nM in MCF7 cells^[2].

Oral administration of Voxtalisib (XL765) 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 (pAKT^T308and pAKT^S473), 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 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, inhibition is also maximal at 4 hours (52%-75%)^[2].

270.29

Solid

C₁₃H₁₄N₆O

934493-76-2

Room temperature in continental US; may vary elsewhere.

DMSO : 10 mg/mL(37.00 mM;Need ultrasonic)

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (3.70 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20%SBE-β-CDin saline)

  Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (3.70 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 1 mg/mL (3.70 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (3.70 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。