RO4929097

製品コードS1575

RO4929097化学構造

分子量(MW):469.4

RO4929097 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.

サイズ 価格(税別)  
JPY 39508.00
JPY 28220.00
JPY 53120.00
JPY 161020.00

カスタマーフィードバック(7)

  • (d,e) Effect of TUG1 overexpression on Nestin activity. Plasmid vectors expressing indicated genes were added to GSC-pE-Nes-222 treated with RO4929097. Phase-contrast and Nestin-EGFP images were shown in (d). Scale bars, 100 μm. (e) Intensity of Nestin-EGFP (left) and number of viable cells (right) compared with the DMSO control were quantified. Viable cells were assessed by trypan blue staining. *P<0.01, Kruskal–Wallis analysis. For all the experimental data, error bars indicate +s.d. (n=3).

    Nat Commun, 2016, 7:13616. RO4929097 purchased from Selleck.

    Western blot analysis of MDA-MB-231 cells treated with CCL2/7/8 or PBS in the presence or absence of a γ-secretase inhibitor (GSI) RO4929097 (10 μmol/L).

    Clin Cancer Res, 2018, 24(10):2370-2382. RO4929097 purchased from Selleck.

  • (F–H) Representative z-projection confocal images of the principal islets in dissected pancreata (post-paraformaldehyde fixation) fromTg(ins:hmgb1-EGFP; β/δ-reporter ) triple transgenic lines treated with DMSO (F), paroxetine (G), or RO4929097 (H). Shown are EGFP+ β-cell nuclei (green) and TagRFP+ δ cells (red); note, PhiYFP in the β/δ-reporter line does not withstand fixation, allowing ‘clean‘ labeling of β-cell nuclei with EGFP. In addition, apparent overlap between the β-cell and δ-cell markers (i.e., occasional ‘yellow‘ cells) is an artifact of z-projection images shown in 2D format. For clarity, the inset panels show a single z-slice image of partial islet showing no co-localization of cell type specific reporters.

    Elife, 2015, doi:10.7554/eLife.08261. RO4929097 purchased from Selleck.

    Stem Cells 2014 32(1), 301-12. RO4929097 purchased from Selleck.

  • Stem Cells 2014 32(1), 301-12. RO4929097 purchased from Selleck.

    left, Increasing doses (0 μmol/L, 3 μmol/L, 30 μmol/L) of GSI RO4929097 inhibits sphere formation in RD and SMS-CTR spheres; right, Expression of YAP5SA in the presence of GSI restores sphere formation.

    Mol Cancer Res, 2017, 15(12):1777-1791. RO4929097 purchased from Selleck.

  • Melanoma growth inhibition by the concomitant treatment with a TKI and the GSI inhibitor RO4929097. WM266-4, K457 and SK-Mel2 human metastatic melanoma cells were treated for four days in culture with a tyrosine kinase inhibitor (TKI at 20 mM), and the GSI RO4929097 (RO at 10 mM), either alone or in combination. All treatments significantly reduced cell growth except for RO4929097 on K457 cells. The highest level of inhibition was observed with TKI in combination with RO4929097. Growth was evaluated by the crystal violet staining.

     

     

    2012 Dr. Barbara Bedogni of Case Western Reserve University. RO4929097 purchased from Selleck.

製品安全説明書

Gamma-secretase阻害剤の選択性比較

生物活性

製品説明 RO4929097 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.
ターゲット
γ secretase [1]
(Cell-free assay)
γ secretase(ICN) [1]
(Cell-free assay)
Aβ40 [1]
(Cell-free assay)
4 nM 5 nM 14 nM
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U87 M33jdWNmdGxiVnnhZoltcXS7IFHzd4F6 NWnabGRDOzBizszN MoLsOEBl M4C3WoRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eR?= M4i5XlI1PDl3OUC3
U87 R1 NVu0OZZ2S2WubDDWbYFjcWyrdImgRZN{[Xl? MXSzNEDPxE1? M{XTSlQh\A>? MVvk[YNz\WG|ZYOgZ4VtdCC4aXHibYxqfHl? NYTSUJlOOjR2OUW5NFc>
MGG4 NHjrcHNE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVPlSJhpOzBizszN NULBOpdyPCCm M1iySYRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eR?= Mn[2NlQ1QTV7MEe=
MGG6 MUjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> M3HudFMxKM7:TR?= MnzCOEBl M13FOIRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eR?= NEfSWIEzPDR7NUmwOy=>
MGG8 MYTD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NY\R[4JROzBizszN MnjpOEBl NX7uWGtu\GWlcnXhd4V{KGOnbHygeoli[mmuaYT5 MmPuNlQ1QTV7MEe=
MGG23 MVjD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MljTN|Ah|ryP NIPMV4s1KGR? NUi2cJQz\GWlcnXhd4V{KGOnbHygeoli[mmuaYT5 NEe1T2czPDR7NUmwOy=>
SUM149 NXPucotQS2WubDDWbYFjcWyrdImgRZN{[Xl? M33HW|AuOTBizszN NHX6R2k4OiCq NHy0VJlqdmirYnn0d{Bk\WyuIHfyc5d1cCCmb4PlJIRmeGWwZHXueIx6 MWmyNlU1PzFyOR?=
Sum190 NHfMUlJE\WyuIG\pZYJqdGm2eTDBd5NigQ>? NVXn[3AxOC1zMDFOwG0> M{[4TFczKGh? MnvGbY5pcWKrdIOgZ4VtdCCpcn;3eIgh\G:|ZTDk[ZBmdmSnboTsfS=> MlzyNlI2PDdzMEm=
WM35 NFXUSYdHfW6ldHnvckBCe3OjeR?= MUixNEB2VQ>? MorwNlQhcA>? Mmf1SG1UVw>? M3TlR4Rm[3KnYYPld{B1cGVibHX2[Yx{KG:oIF7PWGNJKGSxd37zeJJm[W1idHHy[4V1KEiHU{G= M13mUVIyQThyNEC4
WM98.1 M3nQR2Z2dmO2aX;uJGF{e2G7 NVnRXpFOOTBidV2= MYGyOEBp Mm\ISG1UVw>? MUPk[YNz\WG|ZYOgeIhmKGyndnXsd{Bw\iCQT2TDTEBld3ewc4Ty[YFuKHSjcnfleEBJTVNz MnrZNlE6QDB2MEi=
WM115 NGDWblJHfW6ldHnvckBCe3OjeR?= NYPIendtOTBidV2= Mme4NlQhcA>? M3XkSmROW09? M1:0XoRm[3KnYYPld{B1cGVibHX2[Yx{KG:oIF7PWGNJKGSxd37zeJJm[W1idHHy[4V1KEiHU{G= MV:yNVk5ODRyOB?=
WM983A M{\Lb2Z2dmO2aX;uJGF{e2G7 MUmxNEB2VQ>? NInsT28zPCCq MVHEUXNQ NX7PfId2\GWlcnXhd4V{KHSqZTDs[ZZmdHNib3[gUm9VS0hiZH;3cpN1emWjbTD0ZZJo\XRiSFXTNS=> NUPXU5ZEOjF7OEC0NFg>
WM3248  MlW1SpVv[3Srb36gRZN{[Xl? Mlz2NVAhfU1? MXyyOEBp NGXQV|FFVVOR NXj2TYVH\GWlcnXhd4V{KHSqZTDs[ZZmdHNib3[gUm9VS0hiZH;3cpN1emWjbTD0ZZJo\XRiSFXTNS=> M2jBSFIyQThyNEC4
WM35 M2njNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XtWlExKHWP MXOwMVE5KGR? NWPWPGR[TE2VTx?= NHPwSmhqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6 MXqyNVk5ODRyOB?=
WM98.1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NILVfFAyOCC3TR?= NVyxTY1DOC1zODDk M{jqPWROW09? NWrSO3M3cW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? NFvES3YzOTl6MESwPC=>
WM115 NWDxcFdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\PXVExKHWP MWWwMVE5KGR? NWrXfnlTTE2VTx?= NYXKZVdRcW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? M2\1SFIyQThyNEC4
WM983A M4rlbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXr6eJU{OTBidV2= NWLXeldMOC1zODDk M4jIUmROW09? MmD2bY5pcWKrdIOgZ4VtdCCpcn;3eIghfGmvZTDk[ZBmdmSnboTsfS=> NILPc48zOTl6MESwPC=>
WM3248  NH;EfY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVX6ZZhIOTBidV2= NEPScYIxNTF6IHS= M3jMUGROW09? NELLUpFqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6 NFLHU40zOTl6MESwPC=>

他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:[5]
+ 展開

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.
細胞試験: [3]
+ 展開
  • 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.
    (参考用のみ)
動物試験:[1]
+ 展開
  • 動物モデル: Female nude mice bearing Calu-6 cells
  • 製剤: 1.0% Klucel in water with 0.2% Tween 80
  • 投薬量: 3 to 60 mg/kg
  • 投与方法: Oral administration
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 93 mg/mL (198.12 mM)
Ethanol 16 mg/mL (34.08 mM)
Water Insoluble
体内 左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
2% DMSO+30% PEG 300+5% Tween+ddH2O
混合させたのち直ちに使用することを推奨します。
10mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 469.4
化学式

C22H20F5N3O3

CAS No. 847925-91-1
保管
in solvent
別名 N/A

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01269411 Terminated Adult Anaplastic Oligodendroglioma|Adult Brain Stem Glioma|Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Adult Mixed Glioma|Recurrent Adult Brain Tumor National Cancer Institute (NCI) July 2011 Phase 1
NCT01269411 Terminated Adult Anaplastic Oligodendroglioma|Adult Brain Stem Glioma|Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Adult Mixed Glioma|Recurrent Adult Brain Tumor National Cancer Institute (NCI) July 2011 Phase 1
NCT01238133 Terminated Estrogen Receptor Negative|HER2/Neu Negative|Progesterone Receptor Negative|Stage IIA Breast Cancer|Stage IIB Breast Cancer|Stage IIIA Breast Cancer|Stage IIIB Breast Cancer|Stage IIIC Breast Cancer|Triple-Negative Breast Carcinoma National Cancer Institute (NCI) December 2010 Phase 1
NCT01122901 Terminated Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Recurrent Adult Brain Tumor National Cancer Institute (NCI) December 2010 Phase 2
NCT01251172 Withdrawn DS Stage I Plasma Cell Myeloma|DS Stage II Plasma Cell Myeloma|DS Stage III Plasma Cell Myeloma|Refractory Plasma Cell Myeloma National Cancer Institute (NCI) December 2010 Phase 2
NCT01270438 Withdrawn Adenocarcinoma of the Colon|Adenocarcinoma of the Rectum|Recurrent Colon Cancer|Recurrent Rectal Cancer|Stage IVA Colon Cancer|Stage IVA Rectal Cancer|Stage IVB Colon Cancer|Stage IVB Rectal Cancer National Cancer Institute (NCI) December 2010 Phase 2

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

  • * 必須

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/

Gamma-secretaseシグナル伝達経路

Gamma-secretase Inhibitors with Unique Features

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID