- 貨號 Cat. No.
- S1575
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
RO4929097
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
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Price |
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10mM/1mLIn DMSO |
USD 299 |
In stock |
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5mg |
USD 214 |
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10mg |
USD 403 |
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50mg |
USD 1222 |
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200mg |
USD 3112 |
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RO4929097
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
Size |
Price |
Stock |
Quantity |
|
|---|
10mM/1mLIn DMSO |
USD 299 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
5mg |
USD 214 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
10mg |
USD 403 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
50mg |
USD 1222 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
200mg |
USD 3112 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
|
RO4929097
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.
Size |
Price |
Stock |
Quantity |
|
|---|
10mM/1mLIn DMSO |
USD 299 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
5mg |
USD 214 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
10mg |
USD 403 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
50mg |
USD 1222 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
200mg |
USD 3112 |
In stock |
0
1
2
3
4
5
6
7
8
9
10
|
|
Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
Description |
RO4929097 is a γ secretase inhibitor with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch withEC50 of 14 nM and 5 nM, respectively. Phase 2. |
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Targets |
γ secretase |
Aβ40 |
ICN |
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IC50 |
4 nM |
14 nM |
5 nM [1] |
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In vitro |
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.[1] 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. [2]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. [3] |
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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. [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] |
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Features |
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Protocol(Only for Reference)
Kinase Assay: [5]
In vitro potency assays |
After RO4929097 is used, the Aβ peptides are measured by ECL assays using a variety of anti-Aβ antibodies and an Origen 1.5 Analyzer. The 4G8 murine mAb binds an epitope in the Aβ peptide (within amino acids 18–21) that is immediately distal to the α-secretase cleavage site. The G2–10 murine mAb binds the C terminus that is exposed after γ-secretase-mediated cleavage to generate amino acid 40 of the Aβ40 peptide. The FCA3542 rabbit antibody binds the C terminus that is exposed after γ-secretase-mediated cleavage to generate amino acid 42 of the Aβ42 peptide. The 4G8 mAb is biotinylated with biotin-LC-sulfo-N-hydroxysuccinimide-ester. The G2–10 and FCA3542 antibodies are ruthenylated with TAG-N-hydroxysuccinimide ester. Aβ(x-40) is detected with biotinylated 4G8 and ruthenylated G2–10. Aβ(x-42) is detected with biotinylated 4G8 and ruthenylated FCA3542. |
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Cell Assay: [3]
Cell lines |
WM35 and WM98.1 cell lines |
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Concentrations |
10 μM |
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Incubation Time |
DMSO |
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Method |
Primary melanoma cell lines, including WM35 and WM98.1, are seeded at 2.5 × 103 cells per well on a 12-well dish in triplicate. The day after (day 0), the medium is replaced, and DMSO or 10 μM RO4929097 is added and changed every 3-4 days. At the indicated time points, cells are fixed in 10% formalin solution and stored in PBS at 4 °C. At day 18-24, all the plates are stained with crystal violet. After color elution with 10% acetic acid, optical density is read at 590 nm. |
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Animal Study: [1]
Animal Models |
Female nude mice bearing Calu-6 cells |
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Dosages |
3 to 60 mg/kg |
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Administration |
Oral administration |
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Solubility |
30% PEG400/0.5% Tween80/5% propylene glycol 15 mg/mL |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
