Abstract
Hypoxia develops in the majority of solid tumors due to the inability of the existing vascular system to supply the growing tumor mass with adequate amounts of oxygen. A large body of clinical evidence suggests that intratumoral hypoxia correlates with the elevated aggressive behavior of cancer cells and their resistance to therapy, leading to poor patient prognoses. A heterodimeric transcription factor, hypoxia inducible factor-1 (HIF-1), has been shown to orchestrate a large number of molecular events required for the adaptation of tumor cells to hypoxia. Therefore, HIF-1 has become an attractive target for the development of anti-cancer drugs. Here, we highlight some of the recently developed small-molecule inhibitors of HIF-1 function. These drugs disrupt the HIF-1 signaling pathway through a variety of mechanisms, including the inhibition of HIF-1alpha protein synthesis, stabilization, nuclear translocation and HIF-1 transactivation of target genes.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Benzopyrans / pharmacology
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Cell Hypoxia / drug effects
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Heterocyclic Compounds, 4 or More Rings / pharmacology
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Humans
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Hypoxia-Inducible Factor 1 / antagonists & inhibitors*
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Hypoxia-Inducible Factor 1 / physiology
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Microtubules / drug effects
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Microtubules / metabolism
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Models, Biological
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Mustard Compounds / pharmacology
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Neoplasms / drug therapy*
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Neoplasms / metabolism
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Neoplasms / physiopathology
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Phenylpropionates / pharmacology
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Phosphoinositide-3 Kinase Inhibitors
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Signal Transduction / drug effects
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Sirolimus / analogs & derivatives
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Sirolimus / pharmacology
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Topotecan / pharmacology
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Topotecan / therapeutic use
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Tubulin Modulators / pharmacology
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Tubulin Modulators / therapeutic use
Substances
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103D5R
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2-amino-3-(4'-N,N-bis(2-chloroethyl)amino)phenylpropionic acid N-oxide
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Benzopyrans
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Heterocyclic Compounds, 4 or More Rings
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Hypoxia-Inducible Factor 1
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Mustard Compounds
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Phenylpropionates
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Phosphoinositide-3 Kinase Inhibitors
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Tubulin Modulators
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Topotecan
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pleurotin
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Sirolimus