Because of their unique pharmacology and potent biological activity, AIMs are the subject of intensive research at leading institutions such as Dartmouth Medical School, Harvard Medical School, The University of Texas M. D. Anderson Cancer Center, Johns Hopkins University and the Burnham Institute. They are the subject of more than
90 papers in refereed journals, including a recent review in Nature Reviews Cancer.
| Relevant Publications |
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Osburn WO, Yates MS, Dolan PD, Chen S, Liby KT, Sporn MB, Taguchi K, Yamamoto M, and Kensler TW. 2008. Genetic or pharmacologic amplification of nrf2 signaling inhibits acute inflammatory liver injury in mice. Toxicol Sci. 104(1):218-27 |
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Thimmulappa RK, Fuchs RJ, Malhotra D, Scollick C, Traore K, Bream JH, Trush MA, Liby KT, Sporn MB, Kensler TW, and Biswal S. 2006. Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxid Redox Signal. 9(11):1963-70. |
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Liby KT, Yore MM, and Sporn MB. 2007. Triterpenoids and rexinoids as multifunctional agents for the prevention and treatment of cancer. Nat Rev Cancer. 7(5):357-69 |
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Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW, and Biswal S. 2005. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun. 351(4):883-9 |
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Yates MS, Tauchi M, Katsuoka F, Flanders KC, Liby KT, Honda T, Gribble GW, Johnson DA, Johnson JA, Burton NC, Guilarte TR, Yamamoto M, Sporn MB, and Kensler TW. 2007. Pharmacodynamic characterization of chemopreventive triterpenoids as exceptionally potent inducers of Nrf2-regulated genes. Mol Cancer Ther. 6(1):154-62 |
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Dinkova-Kostova AT, Liby KT, Stephenson KK, Holtzclaw WD, Gao X, Suh N, Williams C, Risingsong R, Honda T, Gribble GW, Sporn MB, and Talalay P. 2005. Extremely potent triterpenoid inducers of the phase 2 response: correlations of protection against oxidant and inflammatory stress. Proc Natl Acad Sci U S A. 102(12):4584-9 |
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Ahmad R, Raina D, Meyer C, Kharbanda S, and Kufe D. 2006. Triterpenoid CDDO-Me blocks the NF-kappaB pathway by direct inhibition of IKKbeta on Cys-179. J Biol Chem. 281(47):35764-9 |
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Renal/Cardiovascular Disease
Key Researchers |
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Dr. Anupam Agarwal, University of Alabama at Birmingham |
Relevant Publications |
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Tanaka Y, Aleksunes LM, Goedken MJ, Chen C, Reisman SA, Manautou JE, and Klaassen CD. 2008. Coordinated induction of Nrf2 target genes protects against iron nitrilotriacetate (FeNTA)-induced nephrotoxicity. Toxicol Appl Pharmacol. 231(3):364-73. |
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Liby K, Hock T, Yore MM, Suh N, Place AE, Risingsong R, Williams CR, Royce DB, Honda T, Honda Y, Gribble GW, Hill-Kapturczak N, Agarwal A, and Sporn MB. 2005. The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling. Cancer Res. 65(11):4789-98 |
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Botros FT, Schwartzman ML, Stier CT Jr, Goodman AI, and Abraham NG. 2005. Increase in heme oxygenase-1 levels ameliorates renovascular hypertension. Kidney Int. 68(6):2745-55. |
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Vera T, Kelsen S, Yanes LL, Reckelhoff JF, and Stec DE. 2007. HO-1 induction lowers blood pressure and superoxide production in the renal medulla of angiotensin II hypertensive mice. Am J Physiol Regul Integr Comp Physiol. 292(4):R1472-8. |
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Pradhan A, Umezu M, and Fukagawa M. 2006. Heme-oxygenase upregulation ameliorates angiotensin II-induced tubulointerstitial injury and salt-sensitive hypertension. Am J Nephrol. 26(6):552-61 |
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Agarwal R. 2003. Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade. Am J Physiol Renal Physiol. 284(4):F863-9 |
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| Relevant Publications |
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Thimmulappa RK, Scollick C, Traore K, Yates M, Trush MA, Liby KT, Sporn MB, Yamamoto M, Kensler TW, and Biswal S. 2006. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem Biophys Res Commun. 351(4):883-9 |
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Mix KS, Coon CI, Rosen ED, Suh N, Sporn MB, and Brinckerhoff CE. 2004. Peroxisome proliferator-activated receptor-gamma-independent repression of collagenase gene expression by 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid and prostaglandin 15-deoxy-delta(12,14) J2: a role for Smad signaling. Mol Pharmacol. 65(2):309-18. |
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Mix KS, Mengshol JA, Benbow U, Vincenti MP, Sporn MB, and Brinckerhoff CE. 2001. A synthetic triterpenoid selectively inhibits the induction of matrix metalloproteinases 1 and 13 by inflammatory cytokines. Arthritis Rheum. 44(5):1096-104 |
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Minns LA, Buzoni-Gatel D, Ely KH, Rachinel N, Luangsay S, and Kasper LH. 2004. A novel triterpenoid induces transforming growth factor beta production by intraepithelial lymphocytes to prevent ileitis. Gastroenterology. 127(1):119-26. |
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Fava RA, Elliott S, Raymond L, Mollmark J, Hays E, Honda T, Gribble GW, Sporn MB, Vincenti MP. 2007. The synthetic triterpenoid TP-222 inhibits RANKL stimulation of osteoclastogenesis and matrix metalloproteinase-9 expression. J Rheumatol. 34(5):1058-68 |
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Respiratory Disease
Key Researchers |
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Dr. Pam Davis, Case Western Reserve University |
| Relevant Publications |
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Sussan TE, Rangasamy T, Blake DJ, Malhotra D, El-Haddad H, Bedja D, Yates MS, Kombairaju P, Yamamoto M, Liby KT, Sporn MB, Gabrielson KL, Champion HC, Tuder RM, Kensler TW, and Biswal S. 2009. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc Natl Acad Sci U S A 106(1):250-5 |
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Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, Fryer AD, Yamamoto M, Kensler TW, Tuder RM, Georas SN, and Biswal S. 2005. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J Exp Med. 202(1):47-59 |
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CNS Disease
Key Researchers |
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Dr. Flint Beal, Cornell Medical College |
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Dr. Malu Tansey, The University of Texas Southwestern Medical Center at Dallas |
| Relevant Publications |
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Dumont M, Wille E, Calingasan NY, Tampellini D, Williams C, Gouras GK, Liby K, Sporn M, Flint Beal M, and Lin MT. 2009. Triterpenoid CDDO-methylamide improves memory and decreases amyloid plaques in a transgenic mouse model of Alzheimer's disease. J Neurochem. Feb 7 [Epub ahead of print] |
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Chen PC,
Vargas MR, Pani AK, Smeyne RJ, Johnson DA, Kan YW, and Johnson
JA. 2009. Nrf2-mediated neuroprotection in the MPTP mouse
model of Parkinson's disease: Critical role for the astrocyte. Proc Natl Acad Sci U S A. 106(8):2933-8 |
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| Relevant Publications |
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Sun K, Li M, Konopleva M, Konoplev S, Stephens LC, Kornblau SM, Frolova O, Wilkins DE, Ma W, Welniak LA, Andreeff M, and Murphy WJ.2007. The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and reduces murine early acute graft-versus-host disease mortality.Biol Blood Marrow Transplant. 13(5):521-9 |
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| Relevant
Publications |
|
Liby KT, Yore
MM, and Sporn MB. 2007. Triterpenoids and rexinoids as
multifunctional agents for the prevention and treatment of
cancer.
Nat Rev Cancer. 7(5):357-69 |
|
Liby K, Royce
DB, Williams CR, Risingsong R, Yore MM, Honda T, Gribble GW,
Dmitrovsky E, Sporn TA, and Sporn MB. 2007. The synthetic
triterpenoids CDDO-methyl ester and CDDO-ethyl amide prevent
lung cancer induced by vinyl carbamate in A/J mice.
Cancer Res. Mar 15;67(6):2414-9 |
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Yates MS, Kwak MK, Egner PA, Groopman JD, Bodreddigari S,
Sutter TR, Baumgartner KJ, Roebuck BD, Liby KT, Yore MM, Honda
T, Gribble GW, Sporn MB, and Kensler TW. 2006. Potent
protection against aflatoxin-induced tumorigenesis through
induction of Nrf2-regulated pathways by the triterpenoid
1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole.Cancer
Res. 66(4):2488-94 |
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Ling X,
Konopleva M, Zeng Z, Ruvolo V, Stephens LC, Schober W, McQueen
T, Dietrich M, Madden TL, and Andreeff M. 2007. The novel
triterpenoid C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1,
9-dien-28-oic acid inhibits metastatic murine breast tumor
growth through inactivation of STAT3 signaling.
Cancer Res. 67(9):4210-8 |
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