1222998-36-8
中文名稱
1-[4-[4-(1-氧代丙基)-1-哌嗪基]-3-(三氟甲基)苯基]-9-(3-喹啉基)苯并[H]-1,6-萘啶-2(1H)-酮
英文名稱
Torin 1
CAS
1222998-36-8
分子式
C35H28F3N5O2
分子量
608
MOL 文件
1222998-36-8.mol
更新日期
2025/01/20 11:40:08
1222998-36-8 結構式
基本信息
中文別名
化合物TORIN 1MTORC抑制劑(TORIN1)
1-[4-[4-(1-氧代丙基)-1-哌嗪基]-3-(三氟甲基)苯基]-9
1-[4-[4-(1-氧代丙基)-1-哌嗪基]-3-(三氟甲基)苯基]-9-(3-喹啉基)苯并[H]-1,6-萘啶-2(1H)-酮
英文別名
Torin 1CS-1958
Torin 1, >=98%
TORIN-1
TORIN 1
Torin 1 USP/EP/BP
mTOR Inhibitor XI, Torin1 - Calbiochem
Torin 1 - MTOR inhibitor,potent and selective
1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naph
1-[4-(4-PROPANOYLPIPERAZIN-1-YL)-3-(TRIFLUOROMETHYL)PHENYL]-9-QUINOLIN-3-YLBENZO[H][1,6]NAPHTHYRIDIN-2-ONE
1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one
所屬類別
生物化工：mTOR 抑制劑物理化學性質(zhì)
熔點>223°C (dec.)
沸點817.2±65.0 °C(Predicted)
密度1.362
儲存條件+2C to +8C
溶解度溶于DMSO（高達8mg/ml）。
酸度系數(shù)(pKa)4.19±0.20(Predicted)
形態(tài)黃白色粉末
顏色白色或灰白色
穩(wěn)定性Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months.
常見問題列表
生物活性
Torin 1是一種有效的mTORC1/2抑制劑，IC50為2 nM/10 nM；作用于mTOR比作用于PI3K選擇性高1000倍。體外研究
Torin1 inhibits phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin1 exhibits 1000-fold selectivity for mTOR over PI3K (EC50 = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin1 causes cell cycle arrest through a rapamycin-resistant mechanism that is also independent of mTORC2. Torin1 disrupts mTORC1-dependent phenotypes more completely than rapamycin. Rapamycin-resistant functions of mTORC1 are required for cap-dependent translation. In a recent study, it is reported Torin1 increases neurotensin secretion and gene expression through activation of the MEK/ERK/c-Jun pathway in the human endocrine cell line BON.體內(nèi)研究
Torin1 is efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrates good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and peripheral tissues.生物活性
Torin 1是一種有效的mTORC1/2抑制劑，在無細胞試驗中IC50為2 nM/10 nM；作用于mTOR比作用于PI3K選擇性高1000倍。靶點
| Target | Value |
|
mTORC1
(Cell-free assay) | 2 nM |
|
mTOR
(Cell-free assay) | 4.32 nM |
|
DNA-PK
(Cell-free assay) | 6.34 nM |
|
mTORC2
(Cell-free assay) | 10 nM |
|
p110γ
(Cell-free assay) | 171 nM |
體外研究
Torin1在2和10 nM濃度下分別抑制mTORC1 和mTORC2底物的磷酸化。此外，Torin1對mTOR比對PI3K (EC50 = 1800 nM)的選擇性高1000倍，比對450種其它蛋白激酶的結合選擇性高100倍。 Torin1通過耐rapamycin機制引起細胞周期阻滯，并且其不依賴于mTORC2。Torin1比rapamycin更完全地干擾mTORC1依賴表現(xiàn)型。Cap依賴性翻譯需要mTORC1耐Rapamycin的功能。在近期的一項研究中，據(jù)報道Torin1通過活化人內(nèi)分泌細胞系BON 中MEK/ERK/c-Jun通路，能夠增加神經(jīng)降壓素分泌和基因表達。
體內(nèi)研究
Torin1在20 mg/kg劑量下，在U87MG異種移植模型中是有效的，并且在腫瘤和外周組織中對mTOR下游效應蛋白表現(xiàn)出良好的藥效學抑制作用。