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RO4929097

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Chemical Structure| 847925-91-1 同义名 : RG-4733
CAS号 : 847925-91-1
货号 : A306723
分子式 : C22H20F5N3O3
纯度 : 98+%
分子量 : 469.404
MDL号 : MFCD18384976
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(106.52 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 5 mg/mL clear

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
描述 RO4929097 is a potent and selective γ-secretase inhibitor with IC50 value of 4nM for γ-secretase enzyme assay, as well as EC50 values of 14nM and 5nM for Aβ40 and Notch processing in engineered cell lines, respectively. As γ-secretase is the key component of the enzymatic complex cleaving and activating NOTCH, RO4929097 can also inhibit NOTCH signaling indirectly. Treatment with RO4929097 dose-dependently suppressed the production of intracellular Notch at concentration ranging in 0.1-5μM for 5 days, reduced the expression of the downstream Notch target Hes1 at concentration ranging in 0.1-1μM for 24h, and producd a less transformed morphology in A549 cells. Orally administration of RO4929097 at dose of 3, 10, 30 and 60mg/kg, qd, for 14 days achieved tumor growth inhibition by 66%, 77%, 79% and 88% in the A549 xenograft model. Treatment with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule for a 21-day cycle achieved tumor growth inhibition by 91%. Inhibition of tumor growth remained prolonged and sustained up to 34 days post-treatment with reduced expression of several key angiogenic genes tested.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
MGG23 30 μM Cell Viability Assay 4 d decreases cell viability 24495907
MGG4 30 μM Cell Viability Assay 4 d decreases cell viability 24495907
MGG6 30 μM Cell Viability Assay 4 d decreases cell viability 24495907
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.65mL

2.13mL

1.07mL

21.30mL

4.26mL

2.13mL
参考文献

[1]Luistro L, He W, 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]Huynh C, Poliseno L, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PLoS One. 2011;6(9):e25264.