2-Cyano-3,10-dioxooleana-1,9(11)-dien-28-oic acid anhydride. A novel and highly potent anti-inflammatory and cytoprotective agent

Abstract

2-Cyano-3,10-dioxooleana-1,9(11)-dien-28-oic acid anhydride (CDDO anhydride) has been synthesized, which is the first example of an oleanane triterpenoid anhydride. CDDO anhydride shows potency similar to or higher than the corresponding acid (CDDO) in various in vitro and in vivo assays related to inflammation and carcinogenesis. Notably, preliminary phamacokinetics studies show that CDDO anhydride levels are higher than CDDO levels in mouse tissues and blood. Further evaluation of CDDO anhydride is in progress.

A preliminary evaluation of bardoxolone methyl for the treatment of diabetic nephropathy

“…aspx). However, other modifications may have more superior oral bioavailability to CDDO [15], or the additional ability to cross the blood--brain barrier [16], which may be relevant for other indications, such as neuroprotection.…”

Synthesis of amide-spacered dimers of ursolic and oleanolic acid

“…The number of dimers obtained with an incorporation of the C-28 carboxyl group remains limited probably due to its steric hindrance 15 also found for lupane derived dimers 16 . Only a few dimers holding an amide spacer 13,14,16 have been described so far. These compounds were tested as enzyme inhibitors or antivirals butby and largeno cytotoxic data have been provided for these compounds.…”

Inhibition of mitochondrial LonP1 protease by allosteric blockade of ATP binding and hydrolysis via CDDO and its derivatives

“…CDDO and its derivatives (Fig. 1A) have also been proposed to regulate anti-inflammatory and anti-oxidative stress response pathways (19)(20)(21)(22). Multiple cellular targets are directly inhibited by CDDO derivatives, such as Keap1 (23,24), PPAR (25,26), IB kinase beta (IKK-) (27), Jak1 and Stat3 (28), mTOR (29) and tubulin (30).…”