Molecular Weight (MW)

445.42

Formula

C21H19F4N7

CAS No.

1082949-67-4 (free base);

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 1 mg/mL (2.2 mM)

Water: <1 mg/mL

Ethanol: <1 mg/mL

SMILES

CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3

Synonyms

LYS6K2; LY 2584702; LY-2584702; LY2584702; LYS 6K2; LYS-6K2;

In Vitro

In vitro activity: In HCT116 colon cancer cells, LY2584702 inhibits phosphorylation of the S6 ribosomal protein (pS6) with IC50 of 0.1-0.24 μM. LY2584702 has significant synergistic effects when combined with EGFR inhibitor erlotinib or with the mTOR inhibitor everolimus.

Kinase Assay: LY2584702 Tosylate (also known as LYS6K2) is a novel, selective, orally bioavailable, ATP-competitive p70S6K inhibitor with IC50 of 4 nM.

Cell Assay: LY-2584702 is fully dissolved in 20 mL 10% DMSO and reserved at -80°C. When conducted the experiments in vitro, LY-2584702 is further diluted in 0.5% Tween 80, 5% propylene glycol and 30% PEG400 to reach different DMSO concentrations of 0.1 μM, 0.2 μM, 0.6 μM, and 1.0 μM. Cell Counting Kit-8 (CCK-8) is used to measure the cells proliferation in vitro. Cell lines A549 and SK-MES-1 treated by LY-2584702 for 24 h with different concentrations are seeded in 96-well plates at a density of 5×103 per well, with six repeats. DMSO treated, or in other words, the concentration of LY-2584702 of 0 is used as negative control. Cells absorbance at 450 nm is detected every 24 h after seeding to measure the proliferative activities[

In Vivo

LY2584702 (12.5 mg/kg BID), demonstrates significant antitumor efficacy in both U87MG glioblastoma and HCT116 colon carcinoma xenograft models.

Animal model

Mice

Formulation & Dosage

Dissolved in 0.25% Tween-80 and 0.05% antifoam;12.5 mg/kg twice daily, oral

References

Eur J Cancer. 2014 Mar;50(5):867-75; Eur J Cancer. 2014 Mar;50(5):876-84.