RTA-408

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的 Nrf2 激活剂，可增加 Nrf2 靶基因的表达并减少炎症介质的表达。

A potent Nrf2 activator that increases expression of Nrf2 target genes and decreases expression of inflammatory mediators; dose-dependently reduces NO concentrations with IC50 value of 4.4±1.8 nM in RAW 264.7 cells; also increases p21 levels and JNK phosphorylation.Other Indication Phase 2 Clinical(In Vitro):To evaluate the anti-inflammatory activity of Omaveloxolone (RTA 408), RAW 264.7 mouse macrophage cells are treated with Omaveloxolone for two hours and then IFNγ is added to stimulate NO production and release into the media. Omaveloxolone dose-dependently reduces NO concentrations in the media with an IC50 value of 4.4±1.8 nM. The potency of Omaveloxolone 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 Omaveloxolone, a panel of eight human cell lines derived from tumors of different origin are treated with Omaveloxolone and measured cell growth 72 hours later using the sulforhodamine B (SRB) assay. Omaveloxolone inhibits the growth of all tumor lines with an average GI50 value of 260±74 nM. To determine whether Omaveloxolone induces apoptosis, the panel of tumor cells are treated with Omaveloxolone and the caspase substrate, DEVD-AFC, for 24 hours. Omaveloxolone dose-dependently increases DEVD-AFC cleavage, indicating that Omaveloxolone treatment triggers caspase activation in cancer cells. Caspase-3 and caspase-9 cleavage is also observed by western blot at the same concentrations of Omaveloxolone that increases DEVD-AFC cleavage.(In Vivo):To determine whether Omaveloxolone (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 Omaveloxolone beginning 24 h after TBI. Teatment with Omaveloxolone 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).

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Omaveloxolone

Nuclear Receptor/Transcription Factor

Keap1-Nrf2

Nrf2

Other Indications

Other Disease

1474034-05-3

554.7109

C33H44F2N2O3

>98% (HPLC)

10 mM in DMSO

CC(F)(F)C(N[C@]1(CCC(C)(C[C@@]1([C@]23[H])[H])C)CC[C@@]2(C)[C@]4(C)CCC5C(C)(C)C(C(C#N)=C[C@]5(C)C4=CC3=O)=O)=O

Propanamide, N-(2-cyano-3,12-dioxo-28-noroleana-1,9(11)-dien-17-yl)-2,2-difluoro-

(-20℃)

With Ice Pack

≥ 2 years