1. NF-κB
  2. Keap1-Nrf2

RTA-408 (Synonyms: Omaveloxolone)

Cat. No.: HY-12212 Purity: 98.96%
Handling Instructions

RTA-408 is an antioxidant inflammation modulator (AIM), which activates Nrf2 and suppresses nitric oxide (NO).

For research use only. We do not sell to patients.

RTA-408 Chemical Structure

RTA-408 Chemical Structure

CAS No. : 1474034-05-3

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 134 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
5 mg USD 110 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
10 mg USD 150 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
50 mg USD 450 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
100 mg USD 650 In-stock
Stock in Sweden
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

RTA-408 is an antioxidant inflammation modulator (AIM), which activates Nrf2 and suppresses nitric oxide (NO).

IC50 & Target

Nrf2[1]

In Vitro

To evaluate the anti-inflammatory activity of RTA-408, RAW 264.7 mouse macrophage cells are treated with RTA-408 for two hours and then IFNγ is added to stimulate NO production and release into the media. RTA-408 dose-dependently reduces NO concentrations in the media with an IC50 value of 4.4±1.8 nM. The potency of RTA-408 in this assay is similar to that of Bardoxolone methyl, which has an IC50 value of 1.9±0.8 nM. Nrf2 activation is required for AIM-mediated NO suppression. A decrease in nitric oxide synthase 2 (Nos2) protein levels is observed in bardoxolone methyl-treated RAW 264.7 cells, which is attenuated when Nrf2 mRNA levels are reduced by siRNA. To evaluate the anticancer activity of RTA-408, a panel of eight human cell lines derived from tumors of different origin are treated with RTA-408 and measured cell growth 72 hours later using the sulforhodamine B (SRB) assay. RTA-408 inhibits the growth of all tumor lines with an average GI50 value of 260±74 nM. To determine whether RTA-408 induces apoptosis, the panel of tumor cells are treated with RTA-408 and the caspase substrate, DEVD-AFC, for 24 hours. RTA-408 dose-dependently increases DEVD-AFC cleavage, indicating that RTA-408 treatment triggers caspase activation in cancer cells. Caspase-3 and caspase-9 cleavage is also observed by western blot at the same concentrations of RTA-408 that increases DEVD-AFC cleavage[1].

In Vivo

To determine whether RTA-408 is an effective mitigator of hematopoietic acute radiation syndrome after bone marrow-lethal doses of total-body irradiation (TBI), mice are administered 3 daily injections of 17.5 mg/kg RTA-408 beginning 24 h after TBI. Teatment with RTA-408 results in the 35 day survival of 100% of 7 Gy (LD40/35) TBI mice (P<0.05) and 60% of 7.5 Gy (LD100/13) TBI mice (P<0.0001)[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.8027 mL 9.0137 mL 18.0274 mL
5 mM 0.3605 mL 1.8027 mL 3.6055 mL
10 mM 0.1803 mL 0.9014 mL 1.8027 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

MEFs, PANC-1, A549, A375, A549/NF-κB-Luc and HeLa/NF-κB-Luc cells are cultured in Gibco high glucose DMEM with 10% FBS. G-361 cells are cultured in McCoy’s 5A medium with 10% FBS. All other cell lines are cultured in RPMI 1640 medium with 10% FBS. For growth inhibition assays, cells are plated in duplicate 96-well culture dishes at 3×103 cells per well. The following day, one plate is treated with RTA-408 (200, 400, 600, 800 and 1000 nM) and the other is immediately processed for the sulforhodamine B (SRB) assay (time 0). Cells in the RTA-408-treated plate are processed for the SRB assay 72 hours after the start of treatment. Percentage of growth relative to vehicle-treated cells is calculated. Dose-response curves are plotted in GraphPad Prism and GI50 values are calculated. For cell counting experiments, MEFs are plated in 6-well culture dishes at 5×104 cells per well and treated with RTA-408 the following day. Following treatment, cells are counted using a Vi-CELL XR cell analyzer. For clonogenic assays, wild-type (1×103 cells per well) and Keap1-/- (0.5×103 cells per well) MEFs are seeded in 6-well dishes. Six hours later, MEFs are treated with RTA-408. After seven days, colonies are fixed with a 1:7 solution of acetic acid:MeOH and stained with 0.5% crystal violet in MeOH. Colonies consisting of ≥50 cells are counted[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Mice[2]
For radiation survival experiments, wild-type C57Bl/6 CD45.2 mice (6-8 weeks old) are used. Congenic wild-type C57Bl/6 CD45.1 and C57Bl/6 CD45.1/CD45.2 hybrid host mice are used as recipients in transplantation experiments. RTA-408 stock solutions for vehicle control (DMSO) are prepared within 1 h before injection. RTA-408 (17.5 mg/kg) or DMSO is administered intraperitoneally at 24, 48 and 72 h after irradiation. Whole-body irradiation (7-8 Gy) is performed using a 250-kVp X-ray machine with 50 cm source-to-skin distance and a 2 mm copper filter. The dose rate is approximately 1.4 Gy/min.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

554.71

Formula

C₃₃H₄₄F₂N₂O₃

CAS No.

1474034-05-3

SMILES

O=C1C(C#N)=C[[email protected]@]2(C)[[email protected]](CC[[email protected]]([[email protected]@]3(C)[[email protected]@]4([H])[[email protected]@]5([H])[[email protected]@](CCC(C)(C)C5)(NC(C(F)(F)C)=O)CC3)(C)C2=CC4=O)([H])C1(C)C

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 98.96%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number *

 

Organization name *

Country or Region *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
RTA-408
Cat. No.:
HY-12212
Quantity: