| Field | Specification |
|---|---|
| Target | |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C21H20ClF4N7 |
| SMILES | |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
LY-2584702 hydrochloride selectively and competitively inhibits p70S6K at the ATP-binding site, with an IC50 of 4 nM. In an S6K1 enzyme assay, it showed an IC50 of 2 nM. It has the molecular formula C21H20ClF4N7 and a molecular weight of 481.88 g/mol.
Physical & Chemical Properties
| CAS Number | 1082948-81-9 |
|---|---|
| Molecular Formula | C21H20ClF4N7 |
| Molecular Weight | 481.88 g/mol |
| SMILES | CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3.[H]Cl |
| Target | p70S6K |
| Signaling Pathway | MAPK/ERK Pathway |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target
[1][2]
|
p70S6K 4 nM (IC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with your institution's chemical hygiene plan.
In Vitro
In HCT116 colon cancer cells, LY-2584702 (LY2584702) reduces phosphorylation of the S6 ribosomal protein (pS6), with an IC50 of 0.1-0.24 μM[1]. In an S6K1 enzyme assay, LY-2584702 (LY2584702) has an IC50 of 2 nM, and for pS6 inhibition in cells the IC50=100 nM. At high concentrations, LY-2584702 shows some activity against the S6K-related kinases MSK2 and RSK (enzyme assay IC50=58-176 nM). In EOMA cells, LY-2584702 inhibits S6K activity in a dose-dependent manner, as measured by phosphorylation of its downstream effector S6[2]. LY-2584702 (LY2584702) significantly inhibits A549 proliferation after treatment for over 24 h at 0.1 μM (P<0.05), and the decline becomes more pronounced with longer treatment and/or higher drug concentration (all P<0.05). SK-MES-1 gives similar results, although clear inhibition by LY-2584702 appears only at 0.6 μM (P<0.05), much higher than for A549[3].
In Vivo
In U87MG glioblastoma and HCT116 colon carcinoma xenograft models alike, LY-2584702 demonstrates significant single-agent efficacy at two dose levels, 2.5 mg/kg twice daily (BID) and 12.5 mg/kg BID. At TMED50 (threshold minimum effective dose 50%) (2.3 mg/kg) and TMED90 (10 mg/kg), LY-2584702 achieves statistically significant tumor growth reduction in the HCT116 colon carcinoma xenograft model[1]. To probe S6K function in vivo, shAkt3-expressing EOMA cells are implanted in nu/nu mice and then treated for 14 days with LY-2584702 or Rapamycin. Tumors removed after 14 days show that LY-2584702 inhibits S6 phosphorylation almost as effectively as Rapamycin. Compared with pLKO, loss of Akt3 increases tumor growth. LY-2584702 alone does not significantly affect the growth of pLKO tumors, but LY-2584702 significantly reduces the growth of tumors with shAkt3[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
Cell Assay[3]
Dissolve LY-2584702 fully in 20 mL 10% DMSO and store at -80°C. For in vitro experiments, dilute LY-2584702 further in 0.5% Tween 80, 5% propylene glycol, and 30% PEG400 to reach the following DMSO concentrations: 0.1 μM, 0.2 μM, 0.6 μM, and 1.0 μM. Measure cell proliferation in vitro with Cell Counting Kit-8 (CCK-8). Treat cell lines A549 and SK-MES-1 with LY-2584702 at the different concentrations for 24 h, then seed in 96-well plates at 5×103 per well, with six repeats. Use DMSO-treated cells, i.e., LY-2584702 at 0, as the negative control. Read cell absorbance at 450 nm every 24 h after seeding to assess proliferative activity[3].
Animal Administration[2]
Mice[2] Prepare LY-2584702 in 0.25% Tween-80 and 0.05% antifoam and give orally to mice (12.5 mg/kg twice daily). Inject EOMA cells (0.3×106) subcutaneously into 6- to 8-week-old nu/nu female mice (2 sites/mouse, 4-5 mice/group). Measure tumor size daily. For drug treatment, once tumors reach 0.01 cm3, treat the animals with vehicle control or LY-2584702 (12.5 mg/kg twice daily, oral dosing). Afterward, measure tumor size every 3 to 4 days[2].
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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