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Vistusertib

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	同义名 :	AZD2014
	CAS号 :	1009298-59-2
	货号 :	A386287
	分子式 :	C₂₅H₃₀N₆O₃
	纯度 :	99%+
	分子量 :	462.544
	MDL号 :	MFCD22628784
	存储条件：	粉末 Sealed in dry,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 50 mg/mL(108.1 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
	动物实验配方：	IP 2% DMSO+2% Tween80+30% PEG300+water 2 mg/mL clear PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点	mTOR mTOR, IC50:2.8 nM
描述	The kinase mTOR, belonging to the PIKKs family, which regulate cell growth, cell survival, and autophagy, is a key target in the development of antitumor therapies. It was found that rapamycin and its analogues, the first generation of mtor inhibitor, can activate AKT signaling as a consequence of inhibition of the negative feedback loop downstream of mTORC1. AZD2014 (Vistusertib) is a potent mTORC1/2 inhibitor (IC50 = 2.8 nM, measured by recombinant truncated FLAG-tagged mTOR) and displays a high level of selectivity against other members of the PIKKs [a]. Different from rapamycin, treatment with AZD2014 at 3 to 1000 nM can significantly inhibit mTOR substrates, such as pS6-S235/236, p70S6K-T389 and 4E-BP1 Thr37/46, in a dose dependent manner, as well as no AKT activation, in MCF7 cells. While effectively inhibiting signaling to S6, PRAS40 as well as feedback phosphorylation of AKT, AZD2014 can block proliferation in all cell lines, including everolimus-resistant cells and long-term estrogen-deprived (LTED) everolimus-resistant cells at concentration 200/500 nM. Treatment of 15 mg/kg AZD2014 can induce significant growth inhibition in several hormone therapy–sensitive ERb breast cancer xenograft models like MCF7 and HCC1500, as well as three patient-derived primary explant models BR0555, CTC174, and HBCx3. Up to now, AZD2014 enters Phase 1 trial in solid tumours^[1].
作用机制	AZD2014 is a small-molecule ATP competitive inhibitor of mTOR^[2]

细胞研究
细胞系	浓度	检测类型	检测时间	活动说明	数据源
HEK293 cells		Function assay		Inhibition of recombinant FLAG-tagged mTOR (1362 to 2549) (unknown origin) expressed in HEK293 cells, IC50=2.8 nM	23375793
human MCF7 cells		Function assay		Inhibition of mTORC1 in human MCF7 cells xenografted mouse assessed as modulation substrate	23375793
human MDA-MB-468 cells		Function assay	2 h	Inhibition of mTORC2 in human MDA-MB-468 cells assessed as reduction of AKT phosphorylation at Ser473 after 2 hrs, IC50=0.08 μM	23375793

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.81mL

2.16mL

1.08mL

21.62mL

4.32mL

2.16mL

参考文献

[1]First-in-human phase I trial of the dual mTORC1 and mTORC2 inhibitor AZD2014 in solid tumors.

[2]Pike KG, Malagu K, et al. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6.

[3]Guichard SM, Curwen J, et al. AZD2014, an Inhibitor of mTORC1 and mTORC2, Is Highly Effective in ER+ Breast Cancer When Administered Using Intermittent or Continuous Schedules. Mol Cancer Ther. 2015 Nov;14(11):2508-18.

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靶点

靶点	数值

mTOR	mTOR, IC50:2.8 nM