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Description: LY2584702 Tosylate (also known as LYS6K2), the tosylate salt of LY2584702, is a selective, orally bioavailable, and ATP-competitive p70S6K (ribosomal p70 S6 kinase) inhibitor with potential antitumor activity. It inhibits p70S6K with an IC50 of 4 nM. LY2584702 showed potent antiproliferative activity in vitro and high antitumor efficacy in vivo by inhibiting ribosomal protein S6 Kinase (p70S6K), and preventing phosphorylation of the S6 subunit of ribosomes, thereby inhibiting normal ribosomal function within tumor cells leading to a decrease in protein synthesis and in cellular proliferation.
References: Eur J Cancer. 2014 Mar;50(5):867-75; Eur J Cancer. 2014 Mar;50(5):876-84.
Related CAS: 1082949-67-4 (free base); 1082948-81-9 (HCl); 1082949-68-5 (tosylate)
Molecular Weight (MW)
617.62
Formula
C28H27F4N7O3S
CAS No.
1082949-68-5 (tosylate)
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 7 mg/mL (11.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
SMILES Code
CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3
Synonyms
LYS6K2 tosylate; LY2584702; LY 2584702; LY-2584702; LYS-6K2; LYS 6K2; LY2584702 tosylate
Chemical Name: 4-(4-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine 4-methylbenzenesulfonate
SMILES Code: CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3.OS(=O)(C6=CC=C(C)C=C6)=O
Exact Mass: 445.1638
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2
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.
Lot#: V024101,Purity ≥98%
COA
MSDS
NMR
HPLC
Protein expression of RPS6KB1, p-RPS6KB1, rpS6 and p-rpS6 after the treatment by various LY2584702 concentrations for 24 h. PLoS One. 2017 Aug 9;12(8):e0182891.
Proliferation alteration of NSCLC cell lines with RPS6KB1 dephosphorylation by LY2584702 (CCK-8 analysis). PLoS One. 2017 Aug 9;12(8):e0182891.
Cell cycle distribution of NSCLC cell lines with RPS6KB1 dephosphorylation by LY2584702. PLoS One. 2017 Aug 9;12(8):e0182891.