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Chemical Structure| 847925-91-1 Chemical Structure| 847925-91-1

Structure of RO4929097
CAS No.: 847925-91-1

Chemical Structure| 847925-91-1

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RO4929097 (RG-4733) is a γ secretase inhibitor with an IC50 of 4 nM, inhibiting the cellular processing of Aβ40 and Notch with EC50s of 14 nM and 5 nM, respectively.

Synonyms: RG-4733

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Product Details of RO4929097

CAS No. :847925-91-1
Formula : C22H20F5N3O3
M.W : 469.40
SMILES Code : O=C(N[C@H]1C2=CC=CC=C2C3=CC=CC=C3NC1=O)C(C)(C)C(NCC(F)(F)C(F)(F)F)=O
Synonyms :
RG-4733
MDL No. :MFCD18384976
InChI Key :OJPLJFIFUQPSJR-INIZCTEOSA-N
Pubchem ID :49867930

Safety of RO4929097

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
NCI-H358 5 μM 10 min RO4929097 prevented Notch1 activation and partially rescued E-cadherin from the decrease during EDTA treatment PMC4343190
NCI-H322M 5 μM 10 min RO4929097 prevented Notch1 activation and partially rescued E-cadherin from the decrease during EDTA treatment PMC4343190
T4302 CD133+ cells 100 nM 5 days Assessed the impact of RO4929097 on T4302 CD133+ cells, showing that RO4929097 had only modest impact on cell viability. PMC5785731
T4302 CD133- cells 100 nM 5 days Assessed the impact of RO4929097 on T4302 CD133- cells, showing that these cells were essentially unresponsive to RO4929097. PMC5785731
T4105 CD133+ cells 100 nM 3 days Assessed the impact of RO4929097 on T4105 CD133+ cells, showing that RO4929097 significantly undermined tumor sphere formation. PMC5785731
PANC-1 cells 10 μM 24 h To detect the activity of TGF-β1-Smad2/3-Snail signaling, and it was found that RO4929097 significantly reversed the activation of TGF-β1-Smad2/3-Snail1 signaling by Numb-PRRL overexpression. PMC8866481
Miapaca-2 cells 10 μM 24 h To detect the activity of TGF-β1-Smad2/3-Snail signaling, and it was found that RO4929097 significantly reversed the activation of TGF-β1-Smad2/3-Snail1 signaling by Numb-PRRL overexpression. PMC8866481
mouse primary chondrocytes 20 µM RO4929097 inhibited Notch signaling and reduced the expression of senescence markers in chondrocytes PMC10550997
Human fibroblast-like synoviocytes (FLS) from RA patients 5 μM 24 h To investigate the effect of RO4929097 on Notch1 signaling in RA synoviocytes, results showed that RO4929097 reduced mRNA expression levels of Hey-1 and pro-inflammatory cytokines (TNF-α, IL-6, IL-12, IL-17), while increasing the expression of TGF-β and IL-10. PMC6160763
Chronic lymphocytic leukemia (CLL) cells 0.5 µM 3 and 7 days To evaluate the effect of RO4929097 on CLL cell viability. The results showed that RO4929097 had a minor effect on CLL cell viability after 3 days but significantly reduced CLL cell viability after 7 days. PMC7348714

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Pten knockout mice Oral gavage 10 mg/kg Once daily for 4 weeks RO4929097 treatment significantly reduced tumor growth, decreased tumor malignancy and liver fibrosis, and induced a hepatic differentiation phenotype. PMC4764447
nude mice subcutaneous GBM models oral 30 mg/kg daily for 14 days Assessed the impact of RO4929097 combined with tipifarnib on subcutaneous GBM tumors, showing that the combination significantly reduced tumor growth. PMC5785731
mice posttraumatic OA model intraarticular injection 20 µM every two weeks, until 6 or 10 weeks post-surgery RO4929097 alleviated cartilage degeneration and OA progression, reducing the number of senescent chondrocytes PMC10550997
Mice Collagen-induced arthritis (CIA) model Intraperitoneal injection 1 mg/kg Daily, until the end of the experiment To investigate the effect of RO4929097 on arthritis progression in CIA model mice, results showed that RO4929097 significantly improved clinical outcomes, reduced synovial inflammation, cartilage erosion, and neutrophil infiltration, and increased Treg cell population. PMC6160763
mice intracranial glioma model oral 10 mg/kg daily To evaluate the effect of RO4929097 in combination with oHSV therapy PMC7325527

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.13mL

0.43mL

0.21mL

10.65mL

2.13mL

1.07mL

21.30mL

4.26mL

2.13mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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