Vevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKTand AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation ofAKT. Vevorisertib trihydrochloride hasKdvalues of 1.2 nM and 8.6 nM forAKT1and AKT1-E17K, respectively. Vevorisertib trihydrochloride hasIC₅₀values of 0.55, 0.81, and 1.3 nM forAKT1,AKT2, andAKT3, respectively. Vevorisertib trihydrochloride can be used for the research ofcancer^[1].

Vevorisertib trihydrochloride (0, 12, 33, 111, 333, 1000 nM, 2 hours) inhibits phosphorylation of AKT1-E17K^[1].
Vevorisertib trihydrochloride (1 μM for 2 hours; NIH 3T3 cells are transfected with either pcDNAAKT-WT-GFP or pcDNA-E17K-GFP) inhibits plasma membrane translocation of AKT-WT and AKT1-E17K irrespective of the presence of growth factors^[1].
Vevorisertib trihydrochloride (5 μM) exhibites 57% inhibition of full-length AKT1^[1].
Vevorisertib trihydrochloride (0, 0.012, 0.037, 0.11, 0.33, 1 μM; 2 hours) shows a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160 in cancer cell lines^[1].
Vevorisertib trihydrochloride has anti-proliferative effect on esophageal, breast, and head and neck cancer cells (GI₅₀< 1 μM)^[1].
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines^[1].
Vevorisertib trihydrochloride (MK-4440)/imatinib mesylate (IM) combination shows cell cycle arrest, and increases cell death of gastrointestinal stromal tumor (GIST) cells^[2].
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines^[1]:

Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively^[1].
Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively^[1].
Vevorisertib trihydrochloride reachs C_maxplasma concentrations of ≥2 μM^[1].
Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg^[1].
Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent^[2].

696.11

Solid

C₃₅H₄₁Cl₃N₈O

1416775-08-0

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : 150 mg/mL(215.48 mM;Need ultrasonic)

H₂O : 25 mg/mL(35.91 mM;ultrasonic and warming and heat to 60℃)

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 (sealed storage, away from moisture)。-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: ≥ 5.25 mg/mL (7.54 mM); Clear solution

  此方案可获得 ≥ 5.25 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 52.5 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: ≥ 5.25 mg/mL (7.54 mM); Clear solution

  此方案可获得 ≥ 5.25 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 52.5 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