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PMID: 15341784 Published · ppublish English Journal Article Review

The HIF pathway as a therapeutic target.

Drug discovery today ·Vol. 9 ·No. 16 ·2004-08-15 ·Pages 704-11

Hewitson KS, Schofield CJ

Abstract

Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis. Manipulation of the HIF pathway has potential use for the treatment of ischemic disease and cancer. Unlike HIF-beta, which is constitutively expressed, the levels and activity of the HIF-alpha subunit are regulated by processes involving posttranslational hydroxylation, catalyzed by Fe(II)- and 2-oxoglutarate-dependent oxygenases. This review focuses on the HIF pathway as a therapeutic target.

MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors Down-Regulation Helix-Loop-Helix Motifs Humans Hydroxylation Hypoxia-Inducible Factor 1, alpha Subunit Ischemia/metabolism,therapy Neoplasms/blood supply,metabolism,therapy Protein Subunits Trans-Activators/antagonists & inhibitors,metabolism Transcription Factors/antagonists & inhibitors,metabolism Up-Regulation
Chemicals
Basic Helix-Loop-Helix Transcription Factors HIF1A protein, human Hypoxia-Inducible Factor 1, alpha Subunit Protein Subunits Trans-Activators Transcription Factors endothelial PAS domain-containing protein 1
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hewitson Kirsty S
Oxford Centre for Molecular Sciences and the Department of Chemistry, Chemistry Research Laboratory, Mansfield Road, Oxford, OX1 3TA, UK. kirsty.hewitson@chem.ox.ac.uk
Schofield Christopher J
Article Info
Journal
Drug discovery today
Abbr.
Drug Discov Today
ISSN
1359-6446
Published
2004-08-15
Pages
704-11
Language
English
Region
England
NLM ID
9604391
Subset
IM
Corrections
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