PMID- 16842166
OWN - NLM
STAT- MEDLINE
DCOM- 20060822
LR  - 20190728
IS  - 1381-6128 (Print)
IS  - 1873-4286 (Electronic)
IS  - 1381-6128 (Linking)
VI  - 12
IP  - 21
DP  - 2006
TI  - Natural product-derived small molecule activators of hypoxia-inducible factor-1 
      (HIF-1).
PG  - 2673-88
AB  - Hypoxia-inducible factor-1 (HIF-1) is a key mediator of oxygen homeostasis that 
      was first identified as a transcription factor that is induced and activated by 
      decreased oxygen tension. Upon activation, HIF-1 upregulates the transcription of 
      genes that promote adaptation and survival under hypoxic conditions. HIF-1 is a 
      heterodimer composed of an oxygen-regulated subunit known as HIF-1alpha and a 
      constitutively expressed HIF-1beta subunit. In general, the availability and 
      activity of the HIF-1alpha subunit determines the activity of HIF-1. Subsequent 
      studies have revealed that HIF-1 is also activated by environmental and 
      physiological stimuli that range from iron chelators to hormones. Preclinical 
      studies suggest that HIF-1 activation may be a valuable therapeutic approach to 
      treat tissue ischemia and other ischemia/hypoxia-related disorders. The focus of 
      this review is natural product-derived small molecule HIF-1 activators. Natural 
      products, relatively low molecular weight organic compounds produced by plants, 
      animals, and microbes, have been and continue to be a major source of new drugs 
      and molecular probes. The majority of known natural product-derived HIF-1 
      activators were discovered through the pharmacological evaluation of specifically 
      selected individual compounds. On the other hand, the combination of natural 
      products chemistry with appropriate high-throughput screening bioassays may yield 
      novel natural product-derived HIF-1 activators. Potent natural product-derived 
      HIF-1 activators that exhibit a low level of toxicity and side effects hold 
      promise as new treatment options for diseases such as myocardial and peripheral 
      ischemia, and as chemopreventative agents that could be used to reduce the level 
      of ischemia/reperfusion injury following heart attack and stroke.
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 Pharm Des
JT  - Current pharmaceutical design
JID - 9602487
RN  - 0 (Biological Products)
RN  - 0 (Hypoxia-Inducible Factor 1)
SB  - IM
MH  - Animals
MH  - Biological Products/chemistry/*pharmacology/therapeutic use
MH  - Cardiovascular Diseases/drug therapy/genetics/metabolism
MH  - Gene Expression/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Models, Biological
MH  - Molecular Weight
PMC - PMC2907550
MID - NIHMS216833
EDAT- 2006/07/18 09:00
MHDA- 2006/08/23 09:00
PMCR- 2010/07/21
CRDT- 2006/07/18 09:00
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/08/23 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
PHST- 2010/07/21 00:00 [pmc-release]
AID - 10.2174/138161206777698783 [doi]
PST - ppublish
SO  - Curr Pharm Des. 2006;12(21):2673-88. doi: 10.2174/138161206777698783.