Ly-2584702 hydrochloride is a p70S6K selective ATP competitive inhibitor with IC50 of 4 nM.In the S6K1 enzyme assay, the IC50 of LY-2584702 was 2 nM.

p70 S6K:4 nM, S6K1:2 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 ?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 ?inhibits phosphorylation of the S6 ribosomal protein (pS6) in HCT116 colon cancer cells with an IC50 of 0.1-0.24 μM[1].?In S6K1 enzyme assay, the IC50 of LY-2584702 ?is 2 nM.?For pS6 inhibition in cells, the IC50=100 nM.

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].