CDDO imidazolide

Cas No.:	443104-02-7
Chemical Name:	CDDO Imidazolide
Synonyms:	CDDO Imidazolide;(4aR,6aR,6aS,6bR,8aS,12aS,14bS)-8a-(imidazole-1-carbonyl)-4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile;CDDO Im;TP 235;CDDO-Im;CDDO-Imidazolide;RTA-403;TP-235
SMILES:	CC(C)([C@]1([H])CC[C@@]([C@@]2(CC[C@]3(CCC(C)(C[C@@]3([H])[C@]24[H])C)C(N5C=CN=C5)=O)C)6C)C(C(C#N)=C[C@]1(C)C6=CC4=O)=O
Formula:	C34H43N3O3
M.Wt:	541.72352
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	CDDO-Im (CDDO-imidazolide) is an activator of Nrf2 and PPAR, with Kis of 232 and 344 nM for PPARα and PPARγ.
In Vivo:	CDDO-Im is a potent inhibitor of de novo inducible nitric oxide synthase expression in primary mouse macrophages. Moreover, CDDO-Im inhibits growth of B16 murine melanoma and L1210 murine leukemia cells in vivo. Injection of 10 nM (5.4 μg) of CDDO-Im almost completely blocks the ability of IFN-γ to induce iNOS, and treatment with as little as 1 nmol of CDDO-Im (0.54 μg) is partially effective[1].
In Vitro:	CDDO-Im is highly active in suppressing cellular proliferation of human leukemia and breast cancer cell lines (IC50 approximately 10-30 nM). In U937 leukemia cells, CDDO-Im also induces monocytic differentiation as measured by increased cell surface expression of CD11b and CD36[1]. Treatment with CDDO-Im elevates protein levels of Nrf2, a transcription factor previously shown to bind ARE sequences, and increases expression of a number of antioxidant and detoxification genes regulated by Nrf2[2]. CDDO-Im is one of the most potent synthetic triterpenoids shown to induce growth inhibition and apoptosis in various human cancer cells, including multiple myeloma, lung, pancreas and breast cancer. CDDO-Im treatment markedly induces cell cycle arrest at G2/M-phase and apoptosis in the triple-negative breast cancer cell lines, SUM159 and MDA-MB-231. The CD24−/EpCAM+ cells in SUM159 tumorspheres are significantly inhibited by CDDO-Im treatment. CDDO-Im also significantly decreases sphere forming efficiency and tumorsphere size in both primary and secondary sphere cultures[3].
Cell Assay:	CDDO-Im is dissolved in DMSO. SUM159 and MDA-MB-231 cells are seeded into each well of 96-well plates (1,000 cell/well) and treated the next day with vehicle control or CDDO-Im (1, 10, 50, 100 and 200 nM) for given incubation time. The absorbance is measured with a spectrophotometer to determine cell proliferation rate[3].
Animal Administration:	Mice: Mice are injected i.p. with thioglycollate, and the resulting resident peritoneal macrophages are activated 3 days later with an i.p. injection of IFN-γ. CDDO and CDDO-Im are injected i.p. 30 min after IFN-γ. Macrophages are harvested 10 h later, cultured for 12 h, and then assayed for expression of iNOS protein and production of nitric oxide (NO)[1].
References:	[1]. Place AE, et al. The novel synthetic triterpenoid, CDDO-imidazolide, inhibits inflammatory response and tumor growth in vivo. Clin Cancer Res. 2003 Jul;9(7):2798-806. [2]. Liby K, et al. The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res. 2005 Jun 1;65(11):4789-98. [3]. So JY, et al. A synthetic triterpenoid CDDO-Im inhibits tumorsphere formation by regulating stem cell signaling pathways in triple-negative breast cancer. PLoS One. 2014 Sep 17;9(9):e107616.