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RO4929097

产品编号 T6274 CAS 847925-91-1

别名: RG-4733

RO4929097 (RG-4733) 是 γ secretase 抑制剂，IC50=4 nM，能够抑制细胞内 Aβ40 (EC50:14 nM) 的产生和 Notch (EC50:5 nM) 活性。

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RO4929097, CAS 847925-91-1

规格	价格/CNY	货期
1 mg	￥ 315	现货
2 mg	￥ 447	现货
5 mg	￥ 638	现货
10 mg	￥ 1,170	现货
25 mg	￥ 2,110	现货
50 mg	￥ 3,710	现货
100 mg	￥ 5,350	现货
500 mg	待询	5日内发货
1 mL * 10 mM (in DMSO)	￥ 685	现货

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纯度: 97.68%

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生物活性

化学信息

存储 & 溶解度

参考文献

相关产品

产品描述	RO4929097 (RG-4733), a γ secretase inhibitor (IC50: 4 nM), inhibits cellular processing of Aβ40 and Notch (EC50: 14/5 nM).
靶点活性	Aβ40:14 nM (EC50), Notch:5 nM (EC50), γ-secretase:4 nM
体外活性	RO4929097 strongly inhibited γ-secretase enzyme activity with a 4 nmol/L potency (IC50). Treatment of cells caused a dose-dependent decrease in the amount of Aβ peptides secreted into the culture medium (EC50, 14 nmol/L). The potent in vitro activity of RO4929097 translated into strong dose-dependent inhibition of Notch processing in the Notch cell-based reporter assay (EC50, 5 nmol/L). The potency of RO4929097 in cell-free and cellular assays was in the low nanomolar range with >100-fold selectivity observed with respect to 75 other proteins of various types including receptors, ion channels, and enzymes [1]. RO4929097 downregulated the Notch target genes Hes1, Hey1, and HeyL, and showed a significant reduction in anchorage-independent growth in SUM190 and SUM149. However, the putative self-renewal assay mammosphere formation efficiency was increased with the drug. In the conventional 2D clonogenic assay, RO4929097 (1 μM) significantly sensitized SUM190 cells to ionizing radiation and has a modest radiosensitization effect in SUM149 cells [2]. In human primary melanoma cell lines, RO4929097 decreased the levels of NOTCH transcriptional target HES1. This was accompanied by reduced proliferation and impaired ability to form colonies in soft agar and to organize in tridimensional spheres [3].
体内活性	Oral injection of 3 to 60 mg/kg RO4929097 once daily or twice daily to nude mice bearing A549 NSCLC xenografts for either 7, 14, or 21 days of a 21-day schedule results in significant tumor growth inhibition compared with vehicle-treated animals. The tumor growth inhibition values ranges from 66% to 91%. When mice are treated with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule, treatment initially arouses regression of established A549 tumors. At the end of the 21-day cycle (day 47), tumor growth prevention is still 91% compared with vehicle control mice. Inhibition of tumor growth remains prolonged and sustained up to 34 days post-treatment (day 67). On day 67, these mice are retreated with the same dose of RO4929097 for a second cycle (7 days) until day 74. Importantly, the antitumor effects are sustained after dosing is completed. [1] RO4929097 leads to reduced expression of genes associated with angiogenesis in A549 xenograft model. In contrast, the RO4929097-resistant H460a xenograft displays little change in expression of these genes, underscoring the in vivo anti-angiogenesis mechanism of action of RO4929097.[2] For IL6 and IL8 overexpressing tumors, RO4929097 no longer impacts angiogenesis or the infiltration of tumor associated fibroblasts. [4]
细胞实验	Monolayer cultures of both IBC cell lines were trypsinized into single cells and were seeded into individual wells of a 6-well tissue culture plate (for 2D) or ultralow attachment plates (for 3D, 20,000 cells/ml) in the presence or absence of 1 μM RO4929097. Then the 2D and 3D 6-well plates containing seeded single cells were exposed to increasing doses of irradiation (0, 2, 4, or 6 Gy) 4 hrs after plating. However, SUM149 2D monolayer cells were also pre-treated with 1 μM RO4929097 or vehicle for 24 hours to see if cell contact had an effect. 2D plates were incubated for 14 days and colonies were stained with crystal violet while 3D cells were incubated in mammosphere media for 7 days, the spheres were assessed for proliferation using the MTT assay and those with a size of 50 μM were counted using a Gelcount colony counter. For secondary mammosphere assay, cells from primary mammospheres were dispersed with 0.05% trypsin, seeded in 6-well ultra-low attachment plates (10,000 cells/ml) in mammosphere media and counted after a week. Survival curves were generated using Sigmaplot 8.0 [2].
动物实验	RO4929097 was formulated as a suspension in 1.0% Klucel in water with 0.2% Tween 80 for oral administration. RO4929097-treated mice were orally dosed with suspensions at 3 to 60 mg/kg RO4929097 according to the indicated regimens. In the Calu-6 xenograft model, RO4929097 was dosed at 60 mg/kg/d every other week for 4 weeks (7+/7? × 2 cycles). For all other xenograft models, RO4929097 was dosed once daily at 10 mg/kg for 21 days. Statistical analysis was determined by Mann-Whitney rank-sum test, one-way ANOVA, and post hoc Bonferroni t-test. Differences between groups were considered significant when P ≤ 0.05. A549 tumors from vehicle-treated and selected RO4929097-treated groups were collected and fixed in 10% zinc-formalin overnight, processed, paraffin-embedded, sectioned at 5 μm, and stained with H&E for histopathology assessment. An Olympus BX51 microscope (×40 objective) mounted with a Nikon DS-Fi1 using the NIS-Elements F2.20 program collected the histology pictures. For Western blot analysis, three A549 tumors from each group, 7 (60 mg/kg) or 21 days (3 and 30 mg/kg), were flash-frozen. Collagen type V was detected using the H-200 antibody at a dilution of 1:1,000, and MFAP5 was detected using the antibody at a dilution of 1:1,000 [1].

别名	RG-4733
分子量	469.4
分子式	C22H20F5N3O3
CAS No.	847925-91-1

存储

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度

H2O: Insoluble

DMSO: 86 mg/mL (183.2 mM)

Ethanol: 13 mg/mL (27.7 mM)

溶液配制表

可选溶剂	浓度体积质量	1 mg	5 mg	10 mg	25 mg
DMSO / Ethanol	1 mM	2.1304 mL	10.6519 mL	21.3038 mL	53.2595 mL
	5 mM	0.4261 mL	2.1304 mL	4.2608 mL	10.6519 mL
	10 mM	0.213 mL	1.0652 mL	2.1304 mL	5.3259 mL
	20 mM	0.1065 mL	0.5326 mL	1.0652 mL	2.663 mL
DMSO	50 mM	0.0426 mL	0.213 mL	0.4261 mL	1.0652 mL
DMSO	100 mM	0.0213 mL	0.1065 mL	0.213 mL	0.5326 mL

计算器

摩尔浓度计算器

稀释计算器

配液计算器

分子量计算器

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参考文献

1. Luistro L, et al. Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties. Cancer Res. 2009 Oct 1;69(19):7672-80. 2. Debeb BG, et al. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells. Breast Cancer Res Treat. 2012 Jul;134(2):495-510. 3. Huynh C, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One. 2011;6(9):e25264.

剂量换算

对于不同动物的给药剂量换算，您也可以参考 更多...

体内实验配液计算器

请在以下方框中输入您的动物实验信息后点击计算，可以得到母液配置方法和体内配方的制备方法：比如您的给药剂量是10 mg/kg，每只动物体重20 g，给药体积100 μL，一共给药动物10 只，您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。

母液配置方法：2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 50 μL DMSO 主液，加入 300 μL PEG300，混匀澄清，再加 50 μL Tween 80，混匀澄清，再加 600 μL ddH2O, 混匀澄清。

第一步：请输入动物实验的基本信息

剂量

mg/kg

每只动物体重

给药体积

μL

动物数量

第二步：请输入动物体内配方组成，不同的产品配方组成不同，如有配方需求，可先联系我们提供正确的体内配方。

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计算重置

计算结果如下:

工作液浓度: mg/ml;

母液配置方法: mg 药物溶于 μL DMSO (母液浓度为 mg/mL)，如您需要配置的浓度超过该产品的溶解度，请先与我们联系。

体内配方的制备方法：取 μL DMSO 主液，加入 μL PEG300，混匀澄清，再加 μL Tween 80，混匀澄清，再加 μL ddH₂O, 混匀澄清。

备注:

要按顺序从左向右依次添加助溶剂。可配合物理方法，如涡流、超声波或热水浴使之帮助溶解。

技术支持

您可能有的问题的答案可以在抑制剂处理说明中找到，包括如何准备库存溶液，如何存储产品，以及基于细胞的分析和动物实验需要特别注意的问题。

Keywords

RO4929097 847925-91-1 Neuroscience Proteases/Proteasome Stem Cells Beta Amyloid Gamma-secretase γ-secretase RO-4929097 RG-4733 Notch Inhibitor RO 4929097 RG4733 RG 4733 inhibit Gamma secretase inhibitor

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RO4929097

存储

溶解度

溶液配制表

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参考文献

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剂量换算

体内实验配液计算器

技术支持

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