RO4929097

Catalog No.S1575

RO4929097 Chemical Structure

Molecular Weight(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.

Size Price Stock Quantity  
In DMSO USD 238 In stock
USD 170 In stock
USD 320 In stock
USD 970 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

4 Customer Reviews

  • (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.

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

  • Stem Cells 2014 32(1), 301-12. 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.

Purity & Quality Control

Choose Selective Gamma-secretase Inhibitors

Biological Activity

Description 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.
Targets
γ secretase [1]
(Cell-free assay)
γ secretase(ICN) [1]
(Cell-free assay)
Aβ40 [1]
(Cell-free assay)
4 nM 5 nM 14 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
U87 MnzZR4VtdCCYaXHibYxqfHliQYPzZZk> Moq5N|Ah|ryP M{XOWlQh\A>? MkHZ[IVkemWjc3XzJINmdGxidnnhZoltcXS7 M2XiXFI1PDl3OUC3
U87 R1 NUDWd|JTS2WubDDWbYFjcWyrdImgRZN{[Xl? NEjlbIY{OCEQvF2= M1n4cVQh\A>? MlzG[IVkemWjc3XzJINmdGxidnnhZoltcXS7 Ml\3NlQ1QTV7MEe=
MGG4 MULD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NF;EOFY{OCEQvF2= NWTpR5h5PCCm NH3WOIZl\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdIm= NX;hUHdoOjR2OUW5NFc>
MGG6 MlnKR4VtdCCYaXHibYxqfHliQYPzZZk> NVXCTWh6OzBizszN MUS0JIQ> NGfS[GZl\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdIm= NYD2VHBkOjR2OUW5NFc>
MGG8 NIHLUYVE\WyuIG\pZYJqdGm2eTDBd5NigQ>? MlfoN|Ah|ryP MVG0JIQ> M2rMdIRm[3KnYYPld{Bk\WyuII\pZYJqdGm2eR?= MkjINlQ1QTV7MEe=
MGG23 MWPD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MUKzNEDPxE1? NGrDNJk1KGR? NEfCc3ll\WO{ZXHz[ZMh[2WubDD2bYFjcWyrdIm= Mn7pNlQ1QTV7MEe=
SUM149 MVnD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MWGwMVExKM7:TR?= NUDiR5FKPzJiaB?= MW\pcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 MkfINlI2PDdzMEm=
Sum190 NXvnU5B4S2WubDDWbYFjcWyrdImgRZN{[Xl? NWXjUms4OC1zMDFOwG0> NV3heo5GPzJiaB?= MYfpcohq[mm2czDj[YxtKGe{b4f0bEBld3OnIHTldIVv\GWwdHz5 M3[zR|IzPTR5MUC5
WM35 NV:5[oI{TnWwY4Tpc44hSXO|YYm= Mne2NVAhfU1? MoL3NlQhcA>? MXLEUXNQ MXvk[YNz\WG|ZYOgeIhmKGyndnXsd{Bw\iCQT2TDTEBld3ewc4Ty[YFuKHSjcnfleEBJTVNz NX;heotQOjF7OEC0NFg>
WM98.1 NYfwfpB3TnWwY4Tpc44hSXO|YYm= M1:2b|ExKHWP MlrLNlQhcA>? NW\6TpdpTE2VTx?= NHvwOFdl\WO{ZXHz[ZMhfGinIHzleoVteyCxZjDOU3REUCCmb4fud5Rz\WGvIIThdodmfCCKRWOx MnjzNlE6QDB2MEi=
WM115 NXv3ZZd1TnWwY4Tpc44hSXO|YYm= Mo\ONVAhfU1? NXW0e4l1OjRiaB?= M4TwfGROW09? NWf4OZVZ\GWlcnXhd4V{KHSqZTDs[ZZmdHNib3[gUm9VS0hiZH;3cpN1emWjbTD0ZZJo\XRiSFXTNS=> M1r6bVIyQThyNEC4
WM983A MWrGeY5kfGmxbjDBd5NigQ>? NVnqSod2OTBidV2= MUGyOEBp MWDEUXNQ M3vhNYRm[3KnYYPld{B1cGVibHX2[Yx{KG:oIF7PWGNJKGSxd37zeJJm[W1idHHy[4V1KEiHU{G= NX3MeXRXOjF7OEC0NFg>
WM3248  NHHDNZVHfW6ldHnvckBCe3OjeR?= MlfhNVAhfU1? MWiyOEBp NIrTW2JFVVOR MYHk[YNz\WG|ZYOgeIhmKGyndnXsd{Bw\iCQT2TDTEBld3ewc4Ty[YFuKHSjcnfleEBJTVNz NWfNcIpwOjF7OEC0NFg>
WM35 M2m3cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFO3V28yOCC3TR?= M3XVZ|AuOThiZB?= NXizNol[TE2VTx?= NE[5d4pqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6 MWeyNVk5ODRyOB?=
WM98.1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX[xNEB2VQ>? M1\HPFAuOThiZB?= MYjEUXNQ NYDaNnQ{cW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? MUWyNVk5ODRyOB?=
WM115 NH3t[JBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{HDclExKHWP MkjBNE0yQCCm MmHKSG1UVw>? NWnSeWx3cW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? Ml;XNlE6QDB2MEi=
WM983A NY\jfXYyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVqxNEB2VQ>? NVz6NpB[OC1zODDk Mm\uSG1UVw>? NWXORo0ycW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? MXyyNVk5ODRyOB?=
WM3248  MnXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjYVYwyOCC3TR?= Mn:2NE0yQCCm MXrEUXNQ NX\SW|c4cW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? MmnmNlE6QDB2MEi=

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay:[5]
+ Expand

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.
Cell Research:[3]
+ Expand
  • Cell lines: WM35 and WM98.1 cell lines
  • Concentrations: 10 μM
  • Incubation Time: DMSO
  • 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Female nude mice bearing Calu-6 cells
  • Formulation: 1.0% Klucel in water with 0.2% Tween 80
  • Dosages: 3 to 60 mg/kg
  • Administration: Oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 93 mg/mL (198.12 mM)
Ethanol 16 mg/mL (34.08 mM)
Water Insoluble
In vivo Add solvents individually and in order:
2% DMSO+30% PEG 300+5% Tween+ddH2O
10mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 469.4
Formula

C22H20F5N3O3

CAS No. 847925-91-1
Storage powder
Synonyms N/A

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01236586 Withdrawn Lymphoma|Brain Neoplasms|Sarcoma|Osteosarcoma|Wilms Tumor National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) October 8, 2010 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
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
NCT01189240 Terminated Adult Anaplastic Astrocytoma|Adult Anaplastic Oligodendroglioma|Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Recurrent Adult Brain Tumor National Cancer Institute (NCI) December 2010 Phase 1|Phase 2
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 Active, not recruiting Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Recurrent Adult Brain Tumor National Cancer Institute (NCI) December 2010 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

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

  • Answer:

    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 Signaling Pathway Map

Gamma-secretase Inhibitors with Unique Features

Related Gamma-secretase Products

Tags: buy RO4929097 | RO4929097 supplier | purchase RO4929097 | RO4929097 cost | RO4929097 manufacturer | order RO4929097 | RO4929097 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID