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Design, Synthesis and Mechanistic Studies of Small Molecule Inhibitors of the Hypoxia Inducible Factor Pathway

Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. In 2006, there were 559,888 cancer deaths in the US. Finding effective treatments for cancer is a major challenge among researchers. In solid tumor, hypoxia increases the progression of malignancy and metastasis by promoting angiogenesis. The transcription factor HIF-1 is responsible for the regulation of cellular processes, including glycolysis and angiogenesis. Clinical evidence has determined that expression of HIF-1 is strongly associated with poor patient prognosis. Also, activation of HIF-1 contributes to malignant behavior and therapeutic resistance. In view of these observations, there is a need for anti-cancer treatments that addresses hypoxic related tumors. HIF-1 presents a viable target for inhibition of tumor growth with small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 pathway, as well as mechanistic studies involved in the investigation of the mode of action of these compounds.

Identiferoai:union.ndltd.org:GEORGIA/oai:digitalarchive.gsu.edu:chemistry_diss-1039
Date20 April 2010
CreatorsMooring, Suazette Reid
PublisherDigital Archive @ GSU
Source SetsGeorgia State University
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceChemistry Dissertations

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