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RO4929097

Catalog No.
A4005
γ secretase inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$116.00
In stock
Evaluation Sample
$30.00
In stock
5mg
$110.00
In stock
10mg
$198.00
In stock
50mg
$594.00
In stock
200mg
$1,639.00
In stock
For scientific research use only and should not be used for diagnostic or medical purposes.

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

RO4929097 (CAS 847925-91-1) is a potent, selective small-molecule inhibitor of γ-secretase, an essential protease in the Notch signaling pathway. It inhibits γ-secretase with high specificity (IC50: 4 nM; EC50: 5 nM), showing minimal inhibitory activity against closely related proteases and over 100-fold selectivity versus a broad spectrum of other proteases. By preventing Notch receptor cleavage and subsequent signaling activation, RO4929097 suppresses proliferation and tumorigenesis across various tumor models, including melanoma, breast, colorectal, pancreatic, and lung cancers. Clinical studies have assessed RO4929097 alone or combined with other anticancer agents for advanced solid tumors.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt469.4
Cas No.847925-91-1
FormulaC22H20F5N3O3
Solubility≥23.47 mg/mL in DMSO; insoluble in H2O; ≥45.2 mg/mL in EtOH with ultrasonic
Chemical Name2,2-dimethyl-N-[(7S)-6-oxo-5,7-dihydrobenzo[d][1]benzazepin-7-yl]-N'-(2,2,3,3,3-pentafluoropropyl)propanediamide
SDFDownload SDF
Canonical SMILESCC(C)(C(=O)NCC(C(F)(F)F)(F)F)C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3NC1=O
Shipping ConditionSmall Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]

Cell lines

SUM190 and SUM149 cells

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.

Reaction Conditions

1 μM, 14 days for 2D cultures 7 days for 3D cultures

Applications

After treating with increasing doses of ionizing radiation in the presence or absence of the drug, 2D colonies were allowed to grow for 10–14 days, while the mammospheres were permitted to grow for 1 week. At 1 μM, RO4929097 was able to sensitize adherent cells to radiation with a more significant effect seen in SUM190 than in SUM149 cells. However, the same dose of inhibitor radioprotected cells grown under conditions that favor the enrichment of the cancer stem cells at higher doses of ionizing radiation. This discrepancy between 2D and 3D cultures suggested that cell contact may be needed for a Notch inhibitor to have a significant effect.

Animal experiment: [2]

Animal models

NOD/SCID/IL2gammaR-/- (NOG) mice injected with WM3248 cells

Dosage form

Oral administration, 10 mg/Kg/day for 30 days

Applications

There was a decrease in tumor growth with RO4929097 treatment, which was more appreciable after tumors were extracted for weight assessment. RO4929097-treated tumors also displayed lower expression of putative melanoma stem cell markers CD166, CD271 and JARID1B compared to vehicle-treated ones.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1] Debeb B G, Cohen E N, Boley K, et al. Pre-clinical studies of Notch signaling inhibitor RO4929097 in inflammatory breast cancer cells. Breast cancer research and treatment, 2012, 134(2): 495-510.

[2] Huynh C, Poliseno L, Segura M F, et al. The novel gamma secretase inhibitor RO4929097 reduces the tumor initiating potential of melanoma. PloS one, 2011, 6(9): e25264.

Biological Activity

Description RO4929097 is an inhibitor of γ secretase with IC50 of 4 nM, inhibiting cellular processing of Aβ40 and Notch with EC50 of 14 nM and 5 nM, respectively.
Targets γ secretase Aβ40 ICN      
IC50 4 nM 14 nM 5 nM      

Quality Control

Chemical structure

RO4929097

Related Biological Data

RO4929097
RO4929097 inhibits cell proliferation. The indicated cell lines were treated with DMSO (white circles) or 10 μM RO4929097 (black circles). A representative curve of three independent experiments is reported. ***p<0.001.

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RO4929097

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RO4929097