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LYS6K2(LY2584702) tosylate salt — Datasheet

CAT. NO. DC7943

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ParameterValue
Chemical NameLY2584702 tosylate salt
CAS No.1082949-68-5
Synonyms4-[4-[4-[4-Fluoro-3-(trifluoromethyl)phenyl]-1-methyl-1H-imidazol-2-yl]-1-piperidinyl]-1H-pyrazolo[3,4-d]pyrimidine 4-methylbenzenesulfonate (1:1);LY-2584702 (tosylate salt);LY2584702 tosylate;LY2584702 tosylate salt;4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine;4-methylbenzenesulfonic acid;4-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine p-toluenesulfonate;LYS6K2;1H-Pyrazolo[3,4-d]pyrimidine, 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methyl-1;LY-2584702 tosylate salt
FormulaC28H27F4N7O3S
M.Wt617.624
SMILESS(C1C([H])=C([H])C(C([H])([H])[H])=C([H])C=1[H])(=O)(=O)O[H].FC1C([H])=C([H])C(=C([H])C=1C(F)(F)F)C1=C([H])N(C([H])([H])[H])C(C2([H])C([H])([H])C([H])([H])N(C3C4C([H])=NN([H])C=4N=C([H])N=3)C([H])([H])C2([H])[H])=N1
Purity>98%
Storage2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Biological Activity

LY-2584702 tosylate salt is a selective ATP competitive inhibitor of p70S6K with an IC50 of 4 nM. In S6K1 enzyme assay, the IC50 of LY-2584702 is 2 nM.

In Vitro

LY-2584702 (LY2584702) 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 (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].

In Vivo

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].

References & source

DC Chemicals original product information

Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.

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