1. Neuronal Signaling
    Stem Cell/Wnt
  2. γ-secretase

RO4929097 (Synonyms: RO-4929097; RO 4929097)

Cat. No.: HY-11102 Purity: 98.02%
Handling Instructions

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

For research use only. We do not sell to patients.
RO4929097 Chemical Structure

RO4929097 Chemical Structure

CAS No. : 847925-91-1

Size Price Stock Quantity
Free sample   Apply now  
10 mM * 1 mL in DMSO $121 In-stock
5 mg $110 In-stock
10 mg $200 In-stock
50 mg $590 In-stock
100 mg $1050 In-stock
200 mg   Get quote  
500 mg   Get quote  

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Description

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

IC50 & Target

IC50: 4 nM (γ secretase)

In Vitro

RO4929097 inhibits the production of ICN reducing the expression of the downstream Notch target, Hes1, producing a less transformed morphology in A549 cells. RO4929097 inhibits Notch processing in human tumor-derived cells[1]. RO4929097 (1 µM) inhibits the growth of breast cancer cells, and the inhibition is 20% for SUM149 and 10% for SUM190 cells. RO4929097 does not have a marked effect in invasiveness of SUM149 cells. RO4929097 significantly reduces colony formation by both cell lines with the effect being more notable in SUM149 than by SUM190 cells[2]. RO4929097 inhibits proliferation, anchorage independent growth, and sphere formation of primary melanoma cells in vitro[3].

In Vivo

RO4929097 (3-60 mg/kg, p.o.) results in significant tumor growth inhibition in nude mice bearing A549 NSCLC xenografts, compared with vehicle-treated animals. When mice are treated with 60 mg/kg RO4929097 twice daily with the 7+/14- schedule, treatment initially causes regression of established A549 tumors[1]. RO4929097 impairs the growth of primary melanoma cells in vivo. The percentage of secondary tumors formed by RO4929097-treated cells is lower; the secondary tumors formed by RO4929097-treated cells are smaller; a significant delay in tumor formation by the RO4929097-treated cells compared to the vehicle-treated ones is observed in mice injected with 104 cells in vivo[3].

Clinical Trial
Sponsor Condition Start Date Phase
National Cancer Institute Metastatic colorectal cancer 2010-12-31 Phase 2
National Cancer Institute Multiple myeloma 2010-12-31 Phase 2
University of Colorado at Denver and Health Sciences Center Pancreas tumor 2010-10-31 Phase 2
National Cancer Institute Stage III melanoma 2010-09-30 Phase 2
National Cancer Institute Stage IV melanoma 2010-09-30 Phase 2
National Cancer Institute; The Cancer Institute of New Jersey Prostate tumor 2010-08-31 Phase 2
References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 2.1304 mL 10.6519 mL 21.3038 mL
5 mM 0.4261 mL 2.1304 mL 4.2608 mL
10 mM 0.2130 mL 1.0652 mL 2.1304 mL
Cell Assay
[2]

The IBC cell lines SUM149 and SUM190 are seeded at a density of 5 × 104 cells. The next day, they are treated with vehicle or increasing doses of RO4929097, ranging from 0.1 nM to 10 μM. After 72 hrs, cells are trypsinized and viable cells counted with a hemocytometer. 

Animal Administration
[1]

RO4929097 is formulated as a suspension in 1.0% Klucel in water with 0.2% Tween 80.

RO4929097 is formulated as a suspension in 1.0% Klucel in water with 0.2% Tween 80 for oral administration. RO4929097-treated mice are orally dosed with suspensions at 3 to 60 mg/kg RO4929097 according to the indicated regimens. In the Calu-6 xenograft model, RO4929097 is dosed at 60 mg/kg/d every other week for 4 weeks (7+/7- × 2 cycles). For all other xenograft models, RO4929097 is dosed once daily at 10 mg/kg for 21 days. Statistical analysis is determined by Mann-Whitney rank-sum test, one-way ANOVA, and post hoc Bonferroni t test. Differences between groups are considered significant when P ≤ 0.05. A549 tumors from vehicle-treated and selected RO4929097-treated groups are collected and fixed in 10% zinc-formalin overnight, processed, paraffin-embedded, sectioned at 5 μM, and stained with H&E for histopathology assessment. An Olympus BX51 microscope (×40 objective) mounted with a Nikon DS-Fi1 using the NIS-Elements F2.20 program collected the histology pictures. For Western blot analysis, three A549 tumors from each group, 7 (60 mg/kg) or 21 days (3 and 30 mg/kg), are flash-frozen. Collagen type V is detected using the H-200 antibody at a dilution of 1:1,000, and MFAP5 is detected using the antibody at a dilution of 1:1,000.

References
M.Wt

469.4

Formula

C₂₂H₂₀F₅N₃O₃

CAS No.

847925-91-1

Storage

4°C, stored under nitrogen

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 49 mg/mL

Purity: 98.02%

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Product Name:
RO4929097
Cat. No.:
HY-11102
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