History of Founder’s Synthetic Triterpenoid Discoveries

2013-2020

• CDDO-Imidazolide targets multiple amino acid residues on the Nrf2 adaptor, Keap1.   J. Med. Chem. 63: 9965-9976, 2020.

https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c01088

• Novel synthetic pyridyl analogues of CDDO-Imidazolide are useful new tools in cancer prevention.  Pharmacological Res 100: 135-147, 2015  https://www.sciencedirect.com/science/article/abs/pii/S1043661815001577

• Synthetic triterpenoid induces 15-PGDH expression and suppresses inflammation-driven colon carcinogenesis. J. Clin. Invest 124: 2472-2482, 2014.  https://pubmed.ncbi.nlm.nih.gov/24837432/

  Complete protection against aflatoxin B1-induced liver cancer with a triterpenoid: DNA adduct dosimetry, molecular signature, and genotoxicity threshold. Cancer Prev Res 7:658-665, 2014.  https://pubmed.ncbi.nlm.nih.gov/24662598/

  Targeting Nrf2-mediated gene transcription by extremely potent synthetic triterpenoids attenuate dopaminergic neurotoxicity in the MPTP-mouse model of Parkinson’s disease. Antioxid Redox Signal 18:139-57, 2013  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514006/

2011-2012

• Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol Revs 64:972-1003, 2012.  https://pharmrev.aspetjournals.org/content/64/4/972

• Triterpenoid modulation of IL-17 and Nrf-2 expression ameliorates neuroinflammation and promotes remyelination in autoimmune encephalomyelitis.  Sci Rep 1:201-11, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242013/

• Proteomic analysis shows synthetic oleanane triterpenoid binds to mTOR. PLoS ONE 6(7):e22862. 2011.   https://pubmed.ncbi.nlm.nih.gov/21818401/

• Neuroprotective effect of Nrf2/ARE activators, CDDO-ethylamide and CDDO-trifluoroethylamide in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med 51:88-96, 2011.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109235/

• New synthetic triterpenoids: potent agents for prevention and treatment of tissue injury caused by inflammatory and oxidative stress. J Nat Prod 74:537-545, 2011  https://pubmed.ncbi.nlm.nih.gov/21309592/

  
  
  

2009-2011

• Neuroprotective effect of Nrf2/ARE activators, CDDO-ethylamide and CDDO-trifluoroethylamide in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med 51:88-96, 2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109235/

• The synthetic triterpenoid CDDO-imidazolide suppresses experimental liver metastasis. Clin Exp Metastasis 28:309-317, 2011.  https://mct.aacrjournals.org/content/6/11_Supplement/C21

• Synthetic triterpenoids prolong survival in a transgenic mouse model of pancreatic cancer. Cancer Prev Res 3:1427-1434, 2010. https://pubmed.ncbi.nlm.nih.gov/20959520/

• Anti-inflammatory triterpenoid blocks immune suppressive function of MDSCs and improves immune response in cancer. Clin Cancer Res16:1812-1823, 2010.  https://pubmed.ncbi.nlm.nih.gov/20215551/

• Triterpenoids, CDDO-methylester or CDDO-ethylamide and rexinoids, LG 100268 or NRX194204 for prevention and treatment of lung cancer in mice. Cancer Prev Res 2:1050-1058, 2009. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2818234/

2007-2009

• Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-Imidazolide. Europ J Pharmacol 620:138-144, 2009.  https://pubmed.ncbi.nlm.nih.gov/19698707/

• Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer’s disease. J Neurochem 109:502-512, 2009.  https://pubmed.ncbi.nlm.nih.gov/19200343/

• Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc Natl Acad Sci USA 106:250-255, 2009.  https://pubmed.ncbi.nlm.nih.gov/19104057/

• Prevention and treatment of experimental ER-negative mammary carcinogenesis by the synthetic triterpenoid CDDO-methyl ester and the rexinoid LG100268. Clin Cancer Revs 14:4556-4563, 2008.  https://pubmed.ncbi.nlm.nih.gov/18628471/

• The synthetic oleanane triterpenoid, CDDO-methyl ester, is a potent anti-angiogenic agent.MolCancerTher6:3139-3146,2007.https://mct.aacrjournals.org/content/6/12/3139.full

2005-2007

• Platforms and networks in triterpenoid pharmacology. Drug Develop Res 68:174-182, 2007.  https://onlinelibrary.wiley.com/doi/abs/10.1002/ddr.20179

• Triterpenoids and rexinoids as multifunctional agents for prevention and treatment of cancer. Nat Rev Cancer 7:357-369, 2007.  https://www.nature.com/articles/nrc2129

• The synthetic triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole blocks nuclear factor-kappaB activation through direct inhibition of IkappaB kinase beta. Mol Cancer Ther 5:3232-3239, 2006. 
  https://pubmed.ncbi.nlm.nih.gov/17148759/

• The synthetic triterpenoid CDDO-Imidazolide suppresses STAT phosphorylation and induces apoptosis in myeloma and lung cancer cells.  Clin Cancer Res, 12:4288-4293, 2006.  https://clincancerres.aacrjournals.org/content/12/14/4288.long

• The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling.  Cancer Res 65:4789-4798, 2005.  https://cancerres.aacrjournals.org/content/65/11/4789

2000-2005

• Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress.  Proc Natl Acad Sci USA 102:4584-4589, 2005.  https://www.pnas.org/content/102/12/4584

• Bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance. Blood 103:3158-3169, 2004.  https://pubmed.ncbi.nlm.nih.gov/15070698/

• The novel synthetic triterpenoid, CDDO-Imidazolide, inhibits inflammatory response and tumor growth in vivo.  Clin Cancer Res 9:2798-2806, 2003. https://clincancerres.aacrjournals.org/content/9/7/2798

• The novel synthetic triterpenoid, CDDO-Imidazolide, inhibits inflammatory response and tumor growth in vivo.  Clin Cancer Res 9:2798-2806, 2003. https://clincancerres.aacrjournals.org/content/9/7/2798

• Synthetic oleanane and ursane triterpenoids with modified rings A and C:  A series of highly active inhibitors of nitric oxide production in mouse macrophages.  J Med Chem 43:4233-4246, 2000.  https://pubmed.ncbi.nlm.nih.gov/11063620/

1999-2000

• Novel synthetic oleanane and ursane triterpenoids with various enone functionalities in ring A as inhibitors of nitric oxide production in mouse macrophages.  J Med Chem 43:1866-1877, 2000.  https://pubs.acs.org/doi/abs/10.1021/jm000008j

• A novel synthetic oleanane triterpenoid, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid CDDO), with potent differentiating, anti-proliferative, and anti-inflammatory activity. Cancer Res 59:336-341, 1999.  https://cancerres.aacrjournals.org/content/59/2/336