| 货号 (SKU) | 包装规格 | 是否现货 | 价格 | 数量 |
|---|---|---|---|---|
| R408063-1ml |
1ml |
现货  |
|
| 英文别名 | RG-4733 | Propanediamide, N1-[(7S)-6,7-dihydro-6-oxo-5H-dibenz[b,d]azepin-7-yl]-2,2-dimethyl-N3-(2,2,3,3,3-pentafluoropropyl)- |
|---|---|
| 规格或纯度 | Moligand™, 10mM in DMSO |
| 英文名称 | RO4929097 |
| 生化机理 | RO4929097 (RG-4733) 是一种 γ 分泌酶抑制剂，在无细胞试验中的 IC50 值为 4 nM，可抑制 Aβ40 和 Notch 的细胞处理，EC50 值分别为 14 nM 和 5 nM。第二阶段 |
| 储存温度 | -80℃储存 |
| 运输条件 | 超低温冰袋运输 |
| 作用类型 | 抑制剂 |
| 作用机制 | γ-分泌酶抑制剂 |
| 产品介绍 |
RO4929097 (RG-4733)是一种γ secretase抑制剂，无细胞试验中IC50为4 nM，抑制Aβ40和Notch的细胞加工，EC50分别为14 nM和5 nM。Phase 2。 Information RO4929097 (RG-4733) is aγ secretaseinhibitor withIC50of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch withEC50of 14 nM and 5 nM, respectively. Phase 2. RO4929097 decreases the amount of Aβ peptides secreted into the culture medium in HEK293 cells with EC50 of 14 nM. RO4929097 strongly inhibits Notch processing with EC50 of 5 nM in the Notch cell-based reporter assay. The potency of RO4929097 in cell-free and cellular assays is 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 (CEREP panel). After 5 days of treatment, RO4929097 reduces the production of ICN in the human NSCLC A549 cells inducing a flattened and less transformed tumor cell phenotype in tissue culture. RO4929097 blocks Notch processing in human non-small cell lung carcinoma cells and decreases expression of the Notch transcriptional target gene Hes1. Treatment with RO4929097 reveals a two- to threefold decrease in the expression of direct Notch target genes, Hes1, Hey1, and Heyl in SUM149 and a 3.5- to eightfold decrease in expression in SUM190 cells. RO4929097 modestly inhibits the growth of SUM149 cells in a dose-dependent manner. At a concentration of 1 μM of RO4929097, growth inhibition is 20 % for SUM149 and 10 % for SUM190 cells, relative to vehicle-treated controls. RO4929097 decreases the production of inflammatory cytokines by T-cells. Furthermore, with RO4929097 treatment, there is a shift in favor of TH2 over TH1 cytokines. In addition, T-cell activation induced IL-6 production would be increased with RO4929097. Upon RO4929097 treatment, the selected melanoma cell lines reveals downregulation of NOTCH downstream effector HES1. A decrease in the amount of melanospheres formed upon RO4929097 treatment in primary melanoma cell lines is detected. In vivo 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. 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. For IL6 and IL8 overexpressing tumors, RO4929097 no longer impacts angiogenesis or the infiltration of tumor associated fibroblasts. cell lines：Human osteosarcoma cell line and human lymphoma U937 cells Concentrations：10 μM Incubation Time：DMSO Powder Purity:≥97% |
| IC50 | Notch, IC50: 5 nM |
|---|
| 分子量 | 469.4 |
|---|
| 溶解性 | Solubility (25°C) In vitro DMSO: 27 mg/mL (199.76 mM); Water: 27 mg/mL (199.76 mM); Ethanol: 27 mg/mL |
|---|
| Concentration | 9-11（mmol/L） |
|---|---|
| Proton NMR spectrum | Conforms to Structure |
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