1082949-67-4
1082949-67-4 structure
- Name: LY-2584702
- Chemical Name: 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
- CAS Number: 1082949-67-4
- Molecular Formula: C21H19F4N7
- Molecular Weight: 445.416
- Catalog: Biochemical Inhibitor PI3K/Akt/mTOR inhibitor (PI3K/Akt/mTOR) S6 Kinase Inhibitor
- Create Date: 2017-02-22 05:38:57
- Modify Date: 2024-01-11 18:10:44
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LY-2584702 free base 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.
| Name | 4-[4-[4-[4-fluoro-3-(trifluoromethyl)phenyl]-1-methylimidazol-2-yl]piperidin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine |
|---|---|
| Synonyms |
unii-i4965c6w4o
LY-2584702 LY-2584702 (free base) |
| Description | LY-2584702 free base 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. |
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| Related Catalog | |
| Target |
S6K1:2 nM (IC50) p70S6K:4 nM (IC50) |
| 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]. 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]. |
| 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[3]. |
| Animal Admin | Mice[2] LY-2584702 is prepared in 0.25% Tween-80 and 0.05% antifoam, and administered orally to mice (12.5 mg/kg twice daily). EOMA cells (0.3×106) are injected subcutaneously in 6- to 8-week-old nu/nu female mice (2 sites/mouse, 4-5 mice/group). Tumor size is measured daily. For drug treatment, when tumors reach 0.01 cm3 in size, the animals are treated with vehicle control or LY-2584702 (12.5 mg/kg twice daily, oral dosing). Tumor size is measured every 3 to 4 days[2]. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 665.3±55.0 °C at 760 mmHg |
| Molecular Formula | C21H19F4N7 |
| Molecular Weight | 445.416 |
| Flash Point | 356.2±31.5 °C |
| Exact Mass | 445.163818 |
| PSA | 75.52000 |
| LogP | 3.37 |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.683 |
| Storage condition | -20℃ |