Dartmouth College

Reata Pharmaceuticals, Inc.

University of California

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Rutgers, the State University of New Jersey

Osteoscreen, Inc.

Karen T Liby

Gordon W Gribble

Michael B Sporn

Tadashi Honda

Robert M Kral, Jr

Liangfeng Fu

Colin J Meyer

Evans O Onyango

Martine Cao

Chitra Sundararajan

Melean Visnick

Gregory R Mundy

Nanjoo Suh

Pamela Gehron Robey

A Hari Reddi

Damian Medici

Ross Garrett

Takahiro Niikura

Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl) imidazole and pharmaceutical compositions containing the same are provided.

Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole

Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl) imidazole and pharmaceutical compositions containing the same are provided. The present invention is a tnterpenoid compound of Formula I, or a hydrate, isomer, prodrug or pharmaceutically acceptable salt thereof: wherein one or more of R, R or R is independently a substituted or unsubstituted aryl group, heteroaryl group, cycloalkyl group or heterocyclyl group, and the remaining R groups are hydrogen. The pyridyl analogs of CD-DO-1m 1 have been developed, which are more stable in human plasma and achieve a higher concentration in target tissues such as liver, pancreas, kidney and lungs.

The present invention concerns methods for treating and preventing renal/kidney disease, insulin resistance/diabetes, fatty liver disease, and/or endothelial dysfunction/cardiovascular disease using synthetic triterpenoids, optionally in combination with a second treatment or prophylaxis.

Synthetic triterpenoids and methods of use in the treatment of disease

The present invention provides triterpenoids produced from natural compounds such as oleanolic acid, ursolic acid, betulinic acid, and hederagenin.

Triterpenoids and compositions containing the same

2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid amino acid derivatives having antiinflammatory properties are provided. Pharmaceutical compositions and methods for preventing or treating inflammation or a disease or condition mediated by inflammation are described.

CDDO-Me amino acid conjugates and methods of use

Synthetic triterpenoids and methods of using the same to induce gene expression and differentiation of stem or progenitor cells are provided. Furthermore, the present invention provides methods for producing a cell, such as a stem or progenitor cell, with induced gene expression by contacting a stem or progenitor cell with an effective amount of a synthetic triterpenoid to induce the expression of one or more of SOX9 (Sex determining region Y-box 9), COL2A1 (Type II Collagen (alpha1)), TGF-&#x3b2;I, TGF-p2, TGF-33, BMP2, BMP4, BMPRII (Bone Morphogenic Protein Receptor II), SMAD (Small Mothers Against Decapentaplegic) 3, SMAD4, SMAD6, SMAD7, TIMP (Tissue Inhibitor of Metalloproteinase)-1 or TIMP-2 in the stem or progenitor cell, wherein the stem or progenitor cell is not a mesenchymal stem cell, periosteium cell or osteoprogenitor cell. In one embodiment, the stem or progenitor cell is multipotent.

Synthetic triterpenoids and methods for modulating stem/progenitor cell gene expression

The present invention features the use of a synthetic triterpenoid to induce gene expression and differentiation of stem or progenitor cells in the treatment of bone/cartilage diseases or conditions.

Methods for using synthetic triterpenoids in the treatment of bone or cartilage diseases or conditions

This invention features betulinic acid derivatives having the formula: wherein the variables are defined herein. The invention also provides related compounds and intermediates thereof, as well as pharmaceutical compositions, kits, and articles of manufacture comprising such compounds. Treatment methods and methods of manufacture are also provided.

Betulinic acid derivatives and methods of use thereof

The present invention concerns methods for stimulating the growth and repair of bone and cartilage using synthetic triterpenoids and tricyclic-bis-enones. Examples of suitable triterpenoids include CDDO, CDDO-Me, CDDO-Im, and CDDO-Ethylamide. Examples of tricyclic-bis-enones include TBE-31 and TBE-34.

Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth

This invention describes novel tricyclic-bis-enone derivatives (TBEs), such as TBE-31, TBE-34, TBE-45 and water-soluble TBEs. The methods of preparing these compounds are also disclosed. The inventors demonstrate the ability of these new TBEs to inhibit proliferation of human myeloma cells, inhibit the induction of iNOS in cells stimulated with interferon-&#x3b3;, induce heme oxygenase-1 (HO-1), induce CD11b expression&#x2014;a leukemia differentiation marker, inhibit proliferation of leukemia cells, induce apoptosis in human lung cancer, and induce apoptosis in other cancerous cells. The TBEs of this invention are expected to be useful agents for the treatment and prevention of many diseases, including cancer, neurological disorders, inflammation, and pathologies involving oxidative stress.

Growing community of inventors

West Lebanon, NH, United States of America

Karen T Liby