| CAS |
No.1313881-70-7 |
| 英文名称 |
ARQ-092 |
| 别名 |
ARQ-092;BAL-4815;RO-0094815AlisolB23-monoacetate;23-O-AcetylalisolB;Alisol-B-Monoacetat |
| 分子式 |
C27H24N6 |
| 分子量 |
432.52 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥98% |
| 外观(性状) |
Off-white to yellow Solid |
| 储存条件 |
Powder:-20℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| 运输条件 |
冷藏运输 |
| MDL |
MFCD30187510 |
| SMILES |
C1CC(C1)(C2=CC=C(C=C2)N3C4=C(C=CC(=N4)C5=CC=CC=C5)N=C3C6=C(N=CC=C6)N)N |
| 靶点 |
Akt |
| 通路 |
PI3K/Akt/mTOR |
| 背景说明 |
ARQ-092是一种有效的选择性和变构型 Akt 抑制剂。 |
| 生物活性 |
Miransertib (ARQ-092) is a potent， orally active， selective and allosteric Akt inhibitor with IC50s of 2.7 nM， 14 nM and 8.1 nM for Akt1， Akt2， Akt3， respectively. Miransertib is also a potent the AKT1-E17K mutant protein inhibitor and has the potential for PI3K/AKT-driven tumors and Proteus syndrome research. Miransertib is effective against Leishmania.[1-2] |
| IC50 |
Akt1 2.7 nM (IC50) Leishmania，Akt3 8.1 nM (IC50) Akt2 14 nM (IC50) Akt1 E17K mutant[1-2] |
| In Vitro |
在源自各种肿瘤类型的大量细胞系中，与具有野生型 (wt) PIK3CA/PIK3R1 或PTEN丢失。Miransertib 对 AN3CA 和 A2780 细胞中的 p-Akt (S473) 和 p-Akt (T308) 表现出极好的抑制作用。使用 Miransertib (IC50=0.31 μM) 观察到下游蛋白 p-PRAS40 (T246) 的抑制作用[1]。 Miransertib 对有杜氏利虫和亚马逊利什曼原虫感染的巨噬细胞内的无鞭毛体有抑制作用。Miransertib 还可以增强利什曼原虫感染的巨噬细胞中的 mTOR 依赖性自噬[2]。 |
| In Vivo |
Miransertib (ARQ-092；化合物 21a) 在大鼠 (5 mg/kg) 和猴子 (10 mg/kg) 中显示出良好的绝对口服生物利用度，F 值分别为 62% 和 49%。与猴子相比，大鼠的半衰期更长，大鼠的 t1/2 值为 17 小时，而猴子为 7 小时。在大鼠和猴子中，Cmax 为 198 ng/mL 和 258 ng/mL，AUCinf 为 5496 h ng/mL 和 2960 h ng/mL[1]。 Miransertib (ARQ-092；化合物 21a) 抑制子宫内膜腺癌人异种移植小鼠模型中的肿瘤生长[1]。 |
| 细胞实验 |
Anti-proliferative cellular assays are conducted using the CellTiter Non-Radioactive Cell Proliferation Assay， which utilizes the production of formazan from a tetrazolium compound by live cells. AN3CA and A2780 cells are obtained from the ATCC. AN3CA cells are cultured in DMEM， and A2780 cells are cultured in RPMI. Cells are plated in 96-well plates at 2，000-10，000 cells/well， cultured for 24 h， and treated with the test compound for 72 h at a final DMSO concentration no greater than 0.5% v/v. PMS stock reagent (0.92 mg/mL in DPBS) is diluted 20-fold in MTS stock reagent (2 mg/mL in DPBS)， and this MTS/PMS mixture is diluted 5-fold into each well of the 96-well plate. The plates are incubated for 3-4 h， and the absorbance of formazan is measured at 490 nm. The data are normalized to the untreated controls， the dose-response curves are fit to a four-parameter logistic equation， and the IC50 values are determined. All IC50 values reported are the geometric mean of at least two independent determinations[1]. |
| 动物实验 |
Mice[2] SHP2Y279C/+ mice are used. Only male progeny are used for the experiments herein and all mice are maintained on outbred C57BL6/J backgrounds， backcrossed for more than 10 generations. Either vehicle or Miransertib (100 mg/kg body weight) is then daily administered by oral gavage for 4 weeks. Administration began at 12 weeks of age (after established hypertrophy is indicated)， and continued for 4 weeks， until the mice reach 16 weeks of age. As controls， SHP2+/+ and SHP2Y279C/+ mice are treated with vehicle alone. |
| 数据来源文献 |
[1]. Lapierre JM， et al. Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4，5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable， Selective， and Potent Allosteric AKT Inhibitor. J Med Chem. 2016 Jul 14;59(13):6455-69.
[2]. Devki Nandan， et al. Miransertib (ARQ 092)， an orally-available， selective Akt inhibitor is effective against Leishmania. PLoS One. 2018 Nov 6;13(11):e0206920. |
| 规格 |
1mg 5mg 10mg 25mg 50mg |
| 单位 |
瓶 |
中文
英语
说明书下载
京公网安备 11011202000391号