GSK-690693

AKT is the central node of PI3K/AKT/mTOR pathway. The PH domain and ATP-competitive site are the main target site for research of new compound¹. GSK690693 is an ATP-competitive pan AKT inhibitor with IC50 values of 2, 13 and 9nM for AKT 1, 2, and 3, respectively. Treatment with GSK690693 on concentration of 0.01-10uM cause decreased phosphorylation level of GSK3, p70S6K, and PRAS40 in BT474 breast tumor cells in a dose-dependent manner. GSK690693 can induce accumulation of the FOXO3A, an Akt downstream substrate, in the nucleus at concentration >1uM. In growth inhibition studies, cell lines with higher level of p-AKT showed more sensitivity to GSK690693, such as HCC1954, ZR-75-1, BT474 and LNCaP, etc.. In vivo studies showed maximal tumor growth inhibition of 58% to 75% at the end of dosing period with 30mg/kg/day dose of GSK690693 (i.p.) for 21 days in mice bearing established SKOV-3 ovarian, LNCaP prostate, BT474 and HCC-1954 breast carcinoma xenografts².

溶解方案(细胞实验)

DMSO 中的溶解度 : 20 mg/mL (47.01 mM; 超声助溶 (<60°C); 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (5.88 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。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。"

"方案 二": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: 2 mg/mL (4.70 mM); 澄清溶液; 超声助溶 此方案可获得 2 mg/mL的澄清溶液。以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: 2 mg/mL (4.70 mM); 悬浊液; 超声助溶 此方案可获得 2 mg/mL的均匀悬浊液，悬浊液可用于口服和腹腔注射。以 1 mL 工作液为例，取 100 μL 20.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 一": "请依序添加每种溶剂：20% HP-β-CD/10 mM Citrate pH 2.0Solubility: 10 mg/mL (23.50 mM); 澄清溶液; 超声助溶"