Dactolisib (BEZ235) is an orally active and dual pan-class IPI3KandmTORkinase inhibitor withIC₅₀s of 4 nM/5 nM/7 nM/75 nM, and 20.7 nM forp110α/p110γ/p110δ/p110βandmTOR, respectively. Dactolisib (BEZ235) inhibits bothmTORC1andmTORC2.

Dactolisib (BEZ235) potently inhibits PI3K in an ATP Competitive Manner. Dactolisib (BEZ235) (250 nM) significantly reduced the phosphorylation levels of the mTOR activated kinase p70S6K. Dactolisib (BEZ235) also leads to a reduction of S235/S236P-RPS6 levels with an IC₅₀of 6.5 nM, suggesting that Dactolisib (BEZ235) can directly inhibit the mTOR kinase, as the kinase domain of mTOR is highly homologous to the one of class IA PI3K. The activity of Dactolisib (BEZ235) against mTOR is confirmed using a biochemical mTOR K-LISA assay (IC₅₀, 20.7 nM)^[1]. The IC₅₀s of Dactolisib (BEZ235) for HCT116, DLD-1, and SW480 cell lines are 14.3±6.4, 9.0±1.5, and 12.0±1.6 nM, respectively^[2].

Dactolisib (BEZ235) (45 mg/kg, p.o.) treatment induces colonic tumor regression in a GEM model for sporadic PIK3CA wild-type CRC^[2]. Dactolisib (BEZ235) (45 mg/kg) is administered to MENX rats (n=2 each group) by oral gavage and animals are sacrificed 1 or 6 hours after treatment. Immunostains for P-AKT and P-S6 show considerable reduction of the two proteins, and particularly of P-S6, 6 hours after administration of Dactolisib (BEZ235) when compares with PEG-treated rats. At 6 hours after treatment, the pituitary adenomas of Dactolisib (BEZ235)-treated rats has a proteomic profile significantly different from the tumors of placebo-treated rats^[3].

469.54

Solid

C₃₀H₂₃N₅O

915019-65-7

Room temperature in continental US; may vary elsewhere.

5% TFA : 8.33 mg/mL(17.74 mM;ultrasonic and warming and heat to 60℃)

DMSO : 5 mg/mL(10.65 mM;ultrasonic and warming and heat to 60℃)

DMF : 2 mg/mL(4.26 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： 50%PEG300   50% saline

  Solubility: 12.5 mg/mL (26.62 mM); Suspended solution; Need ultrasonic
• 2.

  请依序添加每种溶剂： 10% 1-Methyl-2-pyrrolidinone    90%PEG300

  Solubility: ≥ 1.1 mg/mL (2.34 mM); Clear solution
• 3.

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

  Solubility: ≥ 0.52 mg/mL (1.11 mM); Clear solution

  此方案可获得 ≥ 0.52 mg/mL (1.11 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 5.2 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
• 4.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 0.52 mg/mL (1.11 mM); Clear solution

  此方案可获得 ≥ 0.52 mg/mL (1.11 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 5.2 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。