1342891-18-2Relevant academic research and scientific papers
INHIBITORS OF HIF AND ANGIOGENESIS
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, (2011/11/06)
Inhibitors of the Hypoxia Inducible Factor (HIF) and angiogenesis and their methods of use including the treatment of cancer, hypoxia related pathologies, disorders leading to ischemia, for example stroke and ischemic heart disease, and non-cancerous angiogenic diseases are provided.
Design and synthesis of novel small-molecule inhibitors of the hypoxia inducible factor pathway
Mooring, Suazette Reid,Jin, Hui,Devi, Narra S.,Jabbar, Adnan A.,Kaluz, Stefan,Liu, Yuan,Van Meir, Erwin G.,Wang, Binghe
, p. 8471 - 8489 (2012/02/03)
Hypoxia, a reduction in partial oxygen pressure, is a salient property of solid tumors. Hypoxia drives malignant progression and metastasis in tumors and participates in tumor resistance to radio- and chemotherapies. Hypoxia activates the hypoxia-inducible factor (HIF) family of transcription factors, which induce target genes that regulate adaptive biological processes such as anaerobic metabolism, cell motility, and angiogenesis. Clinical evidence has demonstrated that expression of HIF-1 is strongly associated with poor patient prognosis and activation of HIF-1 contributes to malignant behavior and therapeutic resistance. Consequently, HIF-1 has become an important therapeutic target for inhibition by small molecules. Herein, we describe the design and synthesis of small molecules that inhibit the HIF-1 signaling pathway. Many of these compounds exhibit inhibitory activity in the nanomolar range. Separate mechanistic studies indicate that these inhibitors do not alter HIF-1 levels but interfere with the ability of HIF-1α/HIF-1β to interact with cofactors p300/CBP to form an active transcriptional complex. (Figure presented)
