LY-2584702 tosylate salt is a selective ATP competitive inhibitor ofp70S6Kwith anIC₅₀of 4 nM. InS6K1enzyme assay, theIC₅₀of LY-2584702 is 2 nM.

LY-2584702 (LY2584702) inhibits phosphorylation of the S6 ribosomal protein (pS6) in HCT116 colon cancer cells with an IC₅₀of 0.1-0.24 μM^[1]. In S6K1 enzyme assay, the IC₅₀of LY-2584702 (LY2584702) is 2 nM. For pS6 inhibition in cells, the IC₅₀=100 nM. LY-2584702 has some activity against the S6K-related kinases MSK2 and RSK at high concentrations (enzyme assay IC₅₀=58-176 nM). LY-2584702 inhibits S6K activity in EOMA cells, as determined by the phosphorylation of its downstream effector S6, in a dose-dependent manner^[2]. Proliferation of A549 is significantly inhibited by LY-2584702 (LY2584702) treating over 24 h at 0.1 μM (P<0.05); and the trend of decline is more conspicuous with longer treatment and/or with the increased drug concentration (all P<0.05). Similar results are also observed in SK-MES-1, although the obvious inhibition is led by LY-2584702 at 0.6 μM (P<0.05), much higher than that of A549^[3].

LY-2584702 demonstrates significant single-agent efficacy in both U87MG glioblastoma and HCT116 colon carcinoma xenograft models at two dose levels of 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID. LY-2584702 demonstrates statistically significant tumour growth reduction at TMED50 (threshold minimum effective dose 50%) (2.3 mg/kg) and TMED90 (10 mg/kg) in the HCT116 colon carcinoma xenograft model^[1]. To examine the role of S6K in vivo, EOMA cells expressing shAkt3 are implanted in nu/nu mice, then treated for 14 days with LY-2584702 or Rapamycin. Analysis of tumors removed after 14 days shows that LY-2584702 inhibits S6 phosphorylation almost as effectively as Rapamycin. Loss of Akt3 increases tumor growth as compared with pLKO. LY-2584702 treatment alone does not significantly affect the growth of pLKO tumors. However, LY-2584702 significantly reduces the growth of tumors with shAkt3^[2].

617.62

Solid

C₂₈H₂₇F₄N₇O₃S

1082949-68-5

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 : 10.25 mg/mL(16.60 mM;Need ultrasonic and warming)

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: ≥ 1 mg/mL (1.62 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.62 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 (1.62 mM); Suspended solution; Need ultrasonic

  此方案可获得 1 mg/mL (1.62 mM) 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 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 (1.62 mM); Clear solution

  此方案可获得 ≥ 1 mg/mL (1.62 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。