( that RTA 402 has potent single-agentan...)Reata's Synthetic Triterpenoids Profiled in Nature Reviews Cancer,Health

that RTA 402 has potent single-agent anti-cancer activity in patients with several different types of tumors, is exceptionally well tolerated with only mild, transient side effects, inhibits the activity of NF-kB and STAT3 (the drug's targets) in human tumors, and is able to suppress levels of tumor promoting cytokines and growth factors (for example, TNF and VEGF) at very low doses. Reata is also advancing a second Synthetic Triterpenoid capable of crossing the blood-brain barrier for neurological indications including multiple sclerosis, Alzheimer's disease, and Parkinson's disease. This agent is in advanced preclinical development.

In the "Nature Reviews Cancer" article, the researchers provide a comprehensive overview of the discovery and activity of these agents. The authors note that Reata's Synthetic Triterpenoids have profound effects on inflammation and the redox state of cells and tissues, as well as being potent anti-proliferative and pro-apoptotic agents. Because of their unique pharmacology, these agents are being studied at leading research institutions and are the subject of more than 50 publications in peer reviewed journals. The article summarizes the current state of this literature. Some highlights of this comprehensive body of research reviewed in the article include the following:

-- How the drugs were optimized to inhibit the de novo synthesis of iNOS and COX2 in normal mouse macrophages. iNOS and COX2 have essential roles in the initiation of inflammation.

-- An explanation of the drugs' molecular targets and mechanism of action. The synthetic triterpenoids are potent inhibitors of transcription factors such as NF-kB and the STATs that are normally activated by reactive oxygen and nitrogen species. Inhibition is achieved by activation of the antioxidant transcription factor Nrf2, which activates the phase 2 genes and reduces cellular levels of reactive oxygen and nitrogen species. In addition, the triterpenoids directly re
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