PF-4708671
| 中文名称 | PF-4708671 |
|---|---|
| 中文同义词 | 2-[[4-(5-乙基-4-嘧啶基)-1-哌嗪基]甲基]-6-(三氟甲基)-1H-苯并咪唑;P70核糖体S6激酶1抑制剂(S6K1抑制剂)(PF-4708671);2-((4-(5-乙基嘧啶-4-基)哌嗪-1-基)甲基)-6-(三氟甲基)-1H-苯并[D]咪唑;PF-4708671,S6K1抑制剂 |
| 英文名称 | PF-4708671 |
| 英文同义词 | 2-[[4-(5-Ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-5-(trifluoromethyl)-1H-benzo[d]imidazole;PF 4708671;PF4708671/PF-4708671;2-[[4-(5-ethyl-4-pyriMidinyl)-1-piperazinyl]Methyl]-6-(trifluoroMethyl)-1H-benziMidazole;PF-04708671;1H-Benzimidazole, 2-[[4-(5-ethyl-4-pyrimidinyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)-;2-[[4-(5-Ethyl-4-pyrimidinyl)-1-piperazinyl]methyl]-6-(trifluoromethyl)-1H-benzimidazole PF-4708671;2-[[4-(5-ethylpyrimidin-4-yl)piperazin-1-yl]methyl]-6-(trifluoromethyl)-1H-benzimidazole |
| CAS号 | 1255517-76-0 |
| 分子式 | C19H21F3N6 |
| 分子量 | 390.41 |
| EINECS号 | |
| 相关类别 | 小分子抑制剂;小分子抑制剂，天然产物;细胞生物学试剂;Akt;mTOR;PI3K;PI3K/Akt/mTOR;Amines;Aromatics;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pfizer Compounds;Pharmaceuticals;API |
| Mol文件 | 1255517-76-0.mol |
| 结构式 |  |
PF-4708671 性质
| 沸点 | 572.8±50.0 °C(Predicted) |
|---|---|
| 密度 | 1.348±0.06 g/cm3(Predicted) |
| 储存条件 | room temp |
| 溶解度 | 二甲基亚砜：≥20mg/mL |
| 形态 | 粉末 |
| 酸度系数(pKa) | 10.20±0.10(Predicted) |
| 颜色 | 米白色 |
PF-4708671是一种细胞渗透性p70 ribosomal S6 kinase(S6K1亚型)抑制剂，在无细胞试验中Ki/IC50为20 nM/160 nM，作用于S6K1比作用于S6K2选择性高400倍，作用于S6K1比作用于MSK1和RSK1/2选择性分别高4和20倍以上，是第一个报道的S6K1特异性抑制剂。
| Target | Value |
|
p70 S6K1
(Cell-free assay) | 160 nM |
PF-4708671是一种哌嗪基嘧啶类似物，是第一个S6K1特异性抑制剂。PF-4708671不显著抑制紧密相关的S6K2亚型或一组其他AGC激酶 (Akt1, Akt2, PKA, PKCα, PKCϵ, PRK2, ROCK2, RSK1, RSK2 或SGK1)的活性。PF-4708671抑制S6K1介导的响应IGF-1（胰岛素样生长因子1）的S6蛋白的磷酸化，对PMA-诱导的底物磷酸化没有作用效果，底物与RSK (p90核糖体S6激酶)和MSK（丝分裂原和应激活化蛋白激酶）激酶高度相关。PF-4708671诱导S6K1的T型环和疏水性基序磷酸化，这种作用依赖于mTORC1 (mTOR复合体1)。PF-4708671不影响mTORC1的活性。
The tumor growth rate in mice treated with the combination of OSI-906+PF-4708671 is significantly slower than that of OSI-906 alone (P=0.0189) or PF4708671 alone (P=0.0165) treated mice. The average tumor volume in the OSI-906+PF-4708671-treated mice is approximately 50% of that in mice treated with OSI-906 (P=0.0056) or PF-4708671 alone (P<0.001) at the end of a 15-day treatment.