RO4929097

別名：RG-4733

製品コード：S1575 純度：99.77%

RO4929097 (RG-4733) is a γ secretase inhibitor with IC50 of 4 nM in a cell-free assay, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively. Phase 2.

CAS No. 847925-91-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 35700	国内在庫あり
5mg	JPY 25500	国内在庫あり
50mg	JPY 118500	国内在庫あり
200mg	JPY 268500	国内在庫なし(納期7~10日)
1g	JPY 718500	国内在庫なし(納期7~10日)

代表番号: 045-509-1970\|電子メール：[email protected] よく尋ねられる質問

文献中Selleckの製品使用例（116）

製品安全説明書

現在のバッチを見る：純度： 99.77%

99.77

RO4929097関連製品

関連ターゲット	gamma-secretase	もっと見る
関連製品	DAPT DBZ (Dibenzazepine) LY411575 Avagacestat (BMS-708163) MK-0752 Semagacestat (LY450139) Nirogacestat (PF-03084014) MDL-28170 L-685,458	もっと見る
関連化合物ライブラリー	FDA-approved Drug Library Natural Product Library Bioactive Compound Library-I Protease Inhibitor Library Ubiquitination Compound Library	もっと見る

Secretase阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	活性情報	PMID
WM98.1	Function Assay	10 uM	24 h	decreases the levels of NOTCH downstream target HES1	21980408
WM35	Function Assay	10 uM	24 h	decreases the levels of NOTCH downstream target HES1	21980408
Sum190	Cell Viability Assay	0-10 μM	72 h	inhibits cell growth dose dependently	22547109
SUM149	Cell Viability Assay	0-10 μM	72 h	inhibits cell growth dose dependently	22547109
MGG23	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
MGG8	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
MGG6	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
MGG4	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
U87 R1	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
U87	Cell Viability Assay	30 μM	4 d	decreases cell viability	24495907
WM115	Function Assay	10 uM	24 h	decreases the levels of NOTCH downstream target HES1	21980408
WM983A	Function Assay	10 uM	24 h	decreases the levels of NOTCH downstream target HES1	21980408
WM3248	Function Assay	10 uM	24 h	decreases the levels of NOTCH downstream target HES1	21980408
WM35	Growth Inhibition Assay	10 uM	0-18 d	inhibits cell growth time dependently	21980408
WM98.1	Growth Inhibition Assay	10 uM	0-18 d	inhibits cell growth time dependently	21980408
WM115	Growth Inhibition Assay	10 uM	0-18 d	inhibits cell growth time dependently	21980408
WM983A	Growth Inhibition Assay	10 uM	0-18 d	inhibits cell growth time dependently	21980408
WM3248	Growth Inhibition Assay	10 uM	0-18 d	inhibits cell growth time dependently	21980408
A673	qHTS assay				29435139
DAOY	qHTS assay				29435139
BT-37	qHTS assay				29435139
BT-12	qHTS assay				29435139
OHS-50	qHTS assay				29435139
SJ-GBM2	qHTS assay				29435139
SK-N-MC	qHTS assay				29435139
NB-EBc1	qHTS assay				29435139
LAN-5	qHTS assay				29435139
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生物活性

製品説明

Targets

γ secretase ^[1] (Cell-free assay)	Notch ^[1] (Cell-free assay)	Aβ40 ^[1] (Cell-free assay)
4 nM	5 nM	14 nM

In Vitro
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]
Kinase Assay	In vitro potency assays
Kinase Assay	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.
細胞実験	細胞株	WM35 and WM98.1 cell lines
	濃度	10 μM
	反応時間	DMSO
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	Hey1 Snail / N-cadherin / Twist / E-cadherin Akt / p-Akt / Notch / IGF1R / FBXW7 NICD / Hes1 / Hes3 / Hes5		29899322
	Growth inhibition assay	Cell viability		30669546

In Vivo
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]
動物実験	動物モデル	Female nude mice bearing Calu-6 cells
	投与量	3 to 60 mg/kg
	投与経路	Oral administration

参考
[1] Luistro L, et al. Cancer Res. 2009, 69(19), 7672-7680. [2] Debeb BG, et al. Breast Cancer Res Treat. 2012. [3] Huynh C, et al. PLoS One. 2011, 6(9), e25264. [4] He W, et al. Mol Oncol. 2011, 5(3), 292-301. [5] Li YM, et al. Proc Natl Acad Sci U S A. 2000, 97(11), 6138-6143. + 展開

参考

+ 展開

化学情報

分子量	469.4	化学式	C₂₂H₂₀F₅N₃O₃
CAS No.	847925-91-1	SDF	Download RO4929097 SDFをダウンロードする
Smiles	CC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3NC1=O
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 94 mg/mL ( (200.25 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 50 mg/mL

Water : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問（FAQ）

質問1:
How about the half-life of RO4929097(S1575)?

回答
For S1575, the half-life is about 20 hours based on the following paper: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869895/

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