| CAS |
No.1082949-67-4 |
| 英文名称 |
LY-2584702 |
| 别名 |
;UNII-I4965C6W4O;依来曲普坦; |
| 分子式 |
C21H19F4N7 |
| 分子量 |
445.42 |
| 溶解性 |
Soluble in DMSO ≥0.5mg/mL(Need ultrasonic) |
| 纯度 |
≥98% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder: 2-8℃，2 years |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD18633220 |
| SMILES |
CN1C=C(C2=CC=C(F)C(C(F)(F)F)=C2)N=C1C3CCN(C4=C5C(NN=C5)=NC=N4)CC3 |
| InChIKey |
FYXRSVDHGLUMHB-UHFFFAOYSA-N |
| InChI |
InChI=1S/C21H19F4N7/c1-31-10-17(13-2-3-16(22)15(8-13)21(23,24)25)29-19(31)12-4-6-32(7-5-12)20-14-9-28-30-18(14)26-11-27-20/h2-3,8-12H,4-7H2,1H3,(H,26,27,28,30) |
| PubChem CID |
25118925 |
| 靶点 |
p70S6K |
| 通路 |
MAPK |
| 背景说明 |
LY-2584702是一种 ATP 竞争性的选择性 p70S6K 抑制剂。 |
| 生物活性 |
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.[1-3] |
| 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[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]. |
| 细胞实验 |
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]. |
| 动物实验 |
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]. |
| 数据来源文献 |
[1]. Tolcher A， et al. A phase I trial of LY2584702 tosylate， a p70 S6 kinase inhibitor， in patients with advanced solid tumors. Eur J Cancer. 2014 Mar;50(5):867-75.
[2]. Phung TL， et al. Akt1 and akt3 exert opposing roles in the regulation of vascular tumor growth. Cancer Res. 2015 Jan 1;75(1):40-50.
[3]. Chen B， et al. Hyperphosphorylation of RPS6KB1， rather than overexpression， predicts worse prognosis in non-small cell lung cancer patients. PLoS One. 2017 Aug 9;12(8):e0182891. |
| 规格 |
5mg |
| 单位 |
瓶 |
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英语
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