PMID- 16515532
OWN - NLM
STAT- MEDLINE
DCOM- 20060420
LR  - 20190911
IS  - 1389-4501 (Print)
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 7
IP  - 3
DP  - 2006 Mar
TI  - Natural product-based inhibitors of hypoxia-inducible factor-1 (HIF-1).
PG  - 355-69
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) regulates the 
      expression of more than 70 genes involved in cellular adaptation and survival 
      under hypoxic stress. Activation of HIF-1 is associated with numerous 
      physiological and pathological processes that include tumorigenesis, vascular 
      remodeling, inflammation, and hypoxia/ischemia-related tissue damage. Clinical 
      studies suggested that HIF-1 activation correlates directly with advanced disease 
      stages and treatment resistance among cancer patients. Preclinical studies 
      support the inhibition of HIF-1 as a major molecular target for antitumor drug 
      discovery. Considerable effort is underway, in government laboratories, industry 
      and academia, to identify therapeutically useful small molecule HIF-1 inhibitors. 
      Natural products (low molecular weight organic compounds produced by plants, 
      microbes, and animals) continue to play a major role in modern antitumor drug 
      discovery. Most of the compounds discovered to inhibit HIF-1 are natural products 
      or synthetic compounds with structures that are based on natural product leads. 
      Natural products have also served a vital role as molecular probes to elucidate 
      the pathways that regulate HIF-1 activity. Natural products and natural 
      product-derived compounds that inhibit HIF-1 are summarized in light of their 
      biological source, chemical class, and effect on HIF-1 and HIF-mediated gene 
      regulation. When known, the mechanism(s) of action of HIF-1 inhibitors are 
      described. Many of the substances found to inhibit HIF-1 are non-druggable 
      compounds that are too cytotoxic to serve as drug leads. The application of 
      high-throughput screening methods, complementary molecular-targeted assays, and 
      structurally diverse chemical libraries hold promise for the discovery of 
      therapeutically useful HIF-1 inhibitors.
FAU - Nagle, Dale G
AU  - Nagle DG
AD  - Department of Pharmacognosy, Research Institute of Pharmaceutical Sciences, 
      School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA. 
      dnagle@olemiss.edu
FAU - Zhou, Yu-Dong
AU  - Zhou YD
LA  - eng
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - R01 CA098787-02/CA/NCI NIH HHS/United States
GR  - R01 CA098787-01A2/CA/NCI NIH HHS/United States
GR  - CA-98787-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Biological Products)
RN  - 0 (Hypoxia-Inducible Factor 1)
SB  - IM
MH  - Animals
MH  - Biological Products/*pharmacology
MH  - Biotransformation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/metabolism
PMC - PMC2908043
MID - NIHMS216830
EDAT- 2006/03/07 09:00
MHDA- 2006/04/21 09:00
PMCR- 2010/07/21
CRDT- 2006/03/07 09:00
PHST- 2006/03/07 09:00 [pubmed]
PHST- 2006/04/21 09:00 [medline]
PHST- 2006/03/07 09:00 [entrez]
PHST- 2010/07/21 00:00 [pmc-release]
AID - 10.2174/138945006776054979 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2006 Mar;7(3):355-69. doi: 10.2174/138945006776054979.