GDC-mTOR inhibitor

GDC-mTOR inhibitor 是一种具有显着选择性的 mTOR 抑制剂，Ki 为 1.5 nM。 GDC-mTOR inhibitor 在细胞和体内药代动力学 (PK)/药效学 (PD) 实验中抑制 mTORC1 和 mTORC2。

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库存: 现货

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数量
2mg

￥1212.00

970.00

- +
5mg

￥2175.00

1740.00

- +
10mg

￥3050.00

2440.00

- +
50mg

￥8100.00

6480.00

- +

已选 0 种 0 瓶

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货号: ajci6042
CAS: 1207358-59-5
别名: N-乙基-N'-[4-[5,6,7,8-四氢-4-[(3S)-3-甲基-4-吗啉基]-7-(2-嘧啶基)吡啶并[3,4-D]嘧啶-2-基]苯基]脲,mTOR inhibitor-1
分子式: C25H30N8O2
分子量: 474.56
纯度: >98%
溶解度: Soluble in DMSO
储存: Store at -20°C
库存: 现货

Background

Description: IC50 Value: 1.5nM (Ki) GDC-mTOR inhibitor is a potent and selective ATP-competitive inhibitor of mTOR. It's derivative drug, GDC-0349, demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models. Abstract: Selective inhibitors of mammalian target of rapamycin (mTOR) kinase based upon saturated heterocycles fused to a pyrimidine core were designed and synthesized. Each series produced compounds with Ki < 10 nM for the mTOR kinase and >500-fold selectivity over closely related PI3 kinases. This potency translated into strong pathway inhibition, as measured by phosphorylation of mTOR substrate proteins and antiproliferative activity in cell lines with a constitutively active PI3K pathway. Two compounds exhibiting suitable mouse PK were profiled in in vivo tumor models and were shown to suppress mTORC1 and mTORC2 signaling for over 12 h when dosed orally. Both compounds were additionally shown to suppress tumor growth in vivo in a PC3 prostate cancer model over a 14 day study.

Protocol

Animal experiment:

Mice[2]Human prostate cancer NCI-PC3 cells are implanted subcutaneously into the right hind flanks of female NCR nude mice (5×106 cells in 100 μL of Hank’s balanced salt solution). Tumors are monitored until they reach a mean tumor volume of approximately 500 mm3. Then similarly sized tumors are randomly assigned to groups (n=4). Compounds are formulated as suspensions in 0.5% methylcellulose/0.2% Tween 80 (MCT) and dosed orally at 25, 50, and 100 mg/kg (100 μL dose/25 g animal). Tumor and plasma samples are harvested at 1, 6, and 10 h postdose.

参考文献:

[1]. Pei Z, et al. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2012 Nov 29;4(1):103-7.
[2]. Koehler MF, et al. Potent, selective, and orally bioavailable inhibitors of the mammalian target of rapamycin kinase domain exhibiting single agent antiproliferative activity. J Med Chem. 2012 Dec 27;55(24):10958-71.