CDDO-EA

Cas No.:	932730-51-3
Chemical Name:	CDDO-EA
Synonyms:	CDDO-EA;CDDO ethyl amide;RTA405;RTA-405;TP319;TP-319
SMILES:	O=C1C(C#N)=C[C@@]2(C)[C@](CC[C@]([C@@]3(C)[C@@]4([H])[C@@]5([H])[C@@](CCC(C)(C)C5)(C(NCC)=O)CC3)(C)C2=CC4=O)([H])C1(C)C
Formula:	C33H46N2O3
M.Wt:	518.72994
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	A potent Nrf2 activator that upregulates Nrf2 expression and resulted in translocation of Nrf2 into the nucleus.
Target:	Nrf2/ARE[1]
In Vivo:	The survival analysis shows that G93A mice treated with CDDO-EA, compared to G93A littermate controls, lives significantly longer. CDDO-EA treatment increases the life-span by 20.6 days from 124.05±3.7 days to 144.72±8.1 days (16.6%) (p<0.001). In CDDO-EA-treated G93A mice, the age of death is 141.4±5.2 days and the duration from the age of onset to the age of death is 57.6±7.6 days, which means that the age of death from onset is prolonged by 17.5 days (43%)[1].
In Vitro:	CDDO-EA potently activates Nrf2/ARE in a cell culture model of ALS and in the G93A SOD1 mouse model of ALS[1]. CDDO-EA is a potent inducer of apoptosis in A549 lung cancer cells, as shown both by PARP cleavage and Annexin staining. CDDO-EA is more potent than CDDO itself as inducers of heme oxygenase-1 (HO-1). In RAW264.7 macrophage-like cells, CDDO-EA is 7-fold more potent than CDDO as suppressors of the ability of IFN-γ to induce iNOS[2].
Cell Assay:	Wild-type and Nrf2−/− mouse embryonic fibroblasts are pre-treated with CDDO-EA or CDDO-TFEA at various concentrations (1, 10 and 100 nM in DMSO) for 18 hours and incubated with 2’,7’-Dichlorodihydrofluorecein diacetate (H2DCFDA) for 30 min. Cells are challenged with 250 µM tBHP for 15-30 min and the mean fluorescence intensity for ~10,000 cells is analyzed by FACSan flow cytometry using a 480-nm excitation wavelength and a 525-nm emission wavelength[1].
Animal Administration:	Mice[1] G93A SOD1 transgenic familial ALS mice (high copy number) B6SJL background strain (G93A SOD1, B6SJL-TgGur1) are used. G93A transgenic mice are assigned randomly to the control (vehicle, mouse chaw only) and to mouse chaw containing either CDDO-EA or CDDO-TFEA (400 mg/kg of food, n=30 in both groups). This dose corresponds to about 80 mg/kg body weight/day, assuming each mouse consumes 5 grams of food per day. We found mice can tolerate this dose. Treatments started at two different time regimens: 1) “Early” at 30 days of age, about two months prior to symptom onset; 2) “At Onset” from the onset of the phenotype (80-90 days of age). A diet consisting of either 400 mg of CDDO-TFEA per kg of food or 400 mg of CDDO-EA per kg of food, and a control lab diet, are prepared by Purina.
References:	[1]. Neymotin A, et al. Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med. 2011 Jul 1;51(1):88-96. [2]. Liby K, et al. The synthetic triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent lung cancer induced by vinyl carbamate in A/J mice. Cancer Res. 2007 Mar 15;67(6):2414-9.