LY-2584702 (LY2584702) suppresses the phosphorylation of S6 ribosomal protein (pS6) in HCT116 colon cancer cells, exhibiting an IC50 of 0.1-0.24 μM[1]. The IC50 for inhibiting pS6 in cells is 100 nM. LY-2584702 exhibits activity against S6K-related kinases MSK2 and RSK at higher concentrations (enzyme assay IC50=58-176 nM). In EOMA cells, LY-2584702 dose-dependently inhibits S6K activity, as evidenced by the reduced phosphorylation of the downstream effector S6[2]. LY-2584702 (LY2584702) significantly reduces A549 cell proliferation after 24 h of treatment at 0.1 μM (P<0.05), with more pronounced effects at higher concentrations and/or longer durations. Similarly, in SK-MES-1 cells, a notable decrease is observed with LY-2584702 at 0.6 μM (P<0.05), a concentration significantly higher than that affecting A549[3].
体内研究
LY-2584702 shows notable efficacy as a single agent in U87MG glioblastoma and HCT116 colon carcinoma xenograft models at doses of 2.5 mg/kg BID (twice daily) and 12.5 mg/kg BID. It significantly reduces tumor growth at TMED50 (threshold minimum effective dose 50%) of 2.3 mg/kg and TMED90 (90% effective dose) of 10 mg/kg in the HCT116 colon carcinoma xenograft model[1].
To investigate the function of S6K in vivo, EOMA cells with shAkt3 expression are implanted into nu/nu mice and treated with LY-2584702 or Rapamycin for 14 days. Post-treatment tumor analysis reveals that LY-2584702 nearly matches Rapamycin in inhibiting S6 phosphorylation. The absence of Akt3 escalates tumor growth compared to pLKO. While LY-2584702 treatment does not markedly influence pLKO tumor growth, it significantly diminishes the growth of shAkt3 tumors[2].
体外研究
LY-2584702 (LY2584702) suppresses the phosphorylation of S6 ribosomal protein (pS6) in HCT116 colon cancer cells, exhibiting an IC50 of 0.1-0.24 μM[1].
The IC50 for inhibiting pS6 in cells is 100 nM. LY-2584702 exhibits activity against S6K-related kinases MSK2 and RSK at higher concentrations (enzyme assay IC50=58-176 nM). In EOMA cells, LY-2584702 dose-dependently inhibits S6K activity, as evidenced by the reduced phosphorylation of the downstream effector S6[2].
LY-2584702 (LY2584702) significantly reduces A549 cell proliferation after 24 h of treatment at 0.1 μM (P<0.05), with more pronounced effects at higher concentrations and/or longer durations. Similarly, in SK-MES-1 cells, a notable decrease is observed with LY-2584702 at 0.6 μM (P<0.05), a concentration significantly higher than that affecting A549[3].
LY-2584702 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Hepa1-6 hepatocytes
1 µM
24 hours
LY blocked the kinase activity of S6K1, thus reducing pS6 expression and significantly decreasing lipid accumulation in hepatocytes.
JCI Insight. 2022 Jul 22;7(14):e150461.
HEK293 cells
20 nM
3 hours
Inhibition of p70S6K, reducing RPS6 phosphorylation at S235/236 and S240/244
J Biol Chem. 2023 Sep;299(9):105154.
Human bone marrow mesenchymal stem cells (BMSC)
1 µM
LY treatment inhibited the differentiation of BMSC into adipocytes, suggesting that LY may reduce adipogenesis by inhibiting S6K1 activity.
JCI Insight. 2022 Jul 22;7(14):e150461.
LY-2584702 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6N mice
High-fat diet-induced obese mouse model
Oral gavage
25 mg/kg
Every 12 hours for 12 weeks
LY treatment significantly reduced body weight gain and fat accumulation in high-fat diet-induced obese mice and ameliorated hepatic steatosis and dyslipidemia.
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