A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma

Mol Endocrinol. 2000 Oct;14(10):1550-6. doi: 10.1210/mend.14.10.0545.


A novel synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), previously reported to have potent differentiating, antiproliferative, and antiinflammatory activities, has been identified as a ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma). CDDO induces adipocytic differentiation in 3T3-L1 cells, although it is not as potent as the full agonist of PPARgamma, rosiglitazone. Binding studies of CDDO to PPARgamma using a scintillation proximity assay give a Ki between 10(-8) to 10(-7) M. In transactivation assays, CDDO is a partial agonist for PPARgamma. The methyl ester of CDDO, CDDO-Me, binds to PPARgamma with similar affinity, but is an antagonist. Like other PPARgamma ligands, CDDO synergizes with a retinoid X receptor (RXR)-specific ligand to induce 3T3-L1 differentiation, while CDDO-Me is an antagonist in this assay. The partial agonism of CDDO and the antagonism of CDDO-Me reflect the differences in their capacity to recruit or displace cofactors of transcriptional regulation; CDDO and rosiglitazone both release the nuclear receptor corepressor, NCoR, from PPARgamma, while CDDO-Me does not. The differences between CDDO and rosiglitazone as either partial or full agonists, respectively, are seen in the weaker ability of CDDO to recruit the coactivator CREB-binding protein, CBP, to PPARgamma. Our results establish the triterpenoid CDDO as a member of a new class of PPARgamma ligands.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Animals
  • CREB-Binding Protein
  • Cell Differentiation / drug effects
  • Drug Synergism
  • Ligands
  • Methylation
  • Mice
  • Nicotinic Acids / pharmacology
  • Nuclear Proteins / metabolism
  • Nuclear Receptor Co-Repressor 1
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / metabolism*
  • Oleanolic Acid / pharmacology
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Retinoic Acid / metabolism
  • Repressor Proteins / metabolism
  • Retinoid X Receptors
  • Rosiglitazone
  • Tetrahydronaphthalenes / pharmacology
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Trans-Activators / metabolism
  • Transcription Factors / agonists
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid
  • Ligands
  • Ncor1 protein, mouse
  • Nicotinic Acids
  • Nuclear Proteins
  • Nuclear Receptor Co-Repressor 1
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Repressor Proteins
  • Retinoid X Receptors
  • Tetrahydronaphthalenes
  • Thiazoles
  • Thiazolidinediones
  • Trans-Activators
  • Transcription Factors
  • Rosiglitazone
  • Oleanolic Acid
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • LG 100268