A66 is a highly specific and selectivep110αinhibitor with anIC₅₀of 32 nM.

A66 is a potent inhibitor of the wild-type and oncogenic forms of p110α but not other class-I PI3K isoforms^[1]. The p110α-specific inhibitor A66 (0.7 μM) induces a 75-80% reduction in focus formation by the highly transforming iSH2 mutants KS459delN, DKRMNS560del, and K379E. The p110α-specific inhibitor A66 reduced phosphorylation of Akt on T308 by all p85 mutants^[2].

The optimal dosing strategy for xenograft studies is determined by investigating the drug pharmacokinetics after a dose of 10 mg/kg of body weight by intraperitoneal injection in CD-1 mice. Despite a short half-life of only 0.42 h, the large C_max(8247 nM) of A66 S that is reached 30 min after dosing ensured that the AUC_0-inf(area under the curve from zero time to infinity) (6809 nMoh) is similar to that of BEZ-235 (7333 nMoh), which has a longer half-life of 2.73 h. Furthermore, the A66 on SK-OV-3 tumour tissue is tested using a single dose of 100 mg/kg of body weight to determine whether a long-lasting effect of the drug could be achieved on target tissues. These studies show that A66 causes a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase, but not of ERK (extracellular-signal-regulated kinase), at both 1 and 6 h after dosing. Levels of A66 in plasma are determined to be 21.1±1.2 μM and 9.1±1.1 μM at 1 and 6 h after drug injection, whereas levels of A66 in the tumor are 22.7±2.1 μM and 16.0±1.3 μM at the same time points^[1].

393.53

Solid

C₁₇H₂₃N₅O₂S₂

1166227-08-2

Room temperature in continental US; may vary elsewhere.

DMSO : 50 mg/mL(127.06 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: ≥ 2.5 mg/mL (6.35 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.35 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (6.35 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.35 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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: ≥ 2.5 mg/mL (6.35 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.35 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 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。