| Small molecule modulators of Keap1-Nrf2-ARE pathway as potential preventive and therapeutic agents. | |
| | |
MedLine Citation:
|
PMID: 22549716 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response elements (ARE) pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation of Nrf2 signaling induces the transcriptional regulation of ARE-dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1-Nrf2-ARE signaling has become an attractive target for the prevention and treatment of oxidative stress-related diseases and conditions including cancer, neurodegenerative, cardiovascular, metabolic, and inflammatory diseases. Over the last few decades, numerous Nrf2 inducers have been developed and some of them are currently undergoing clinical trials. Recently, overactivation of Nrf2 has been implicated in cancer progression as well as in drug resistance to cancer chemotherapy. Thus, Nrf2 inhibitors could potentially be used to improve the effectiveness of cancer therapy. Herein, we review the signaling mechanism of Keap1-Nrf2-ARE pathway, its disease relevance, and currently known classes of small molecule modulators. We also discuss several aspects of Keap1-Nrf2 interaction, Nrf2-based peptide inhibitor design, and the screening assays currently used for the discovery of direct inhibitors of Keap1-Nrf2 interaction. |
| | |
Authors:
|
Sadagopan Magesh; Yu Chen; Longqin Hu |
Related Documents
:
|
8839566 - Native american cancer conference iii. cognitive correlates and impressions of attendees. 22683426 - Identifying and exploiting defects in the fanconi anemia/brca pathway in oncology. 20097836 - Cancer, culture, and health disparities: time to chart a new course? 18853416 - Neuroendocrine tumor epidemiology: contrasting norway and north america. 21853236 - Laparoscopic-assisted low and ultralow anterior resection for lower rectal cancer using... 21943816 - Association between hla-dqa1, hla-dqb1 and oral cancer. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2012-05-01 |
Journal Detail:
|
Title: Medicinal research reviews Volume: 32 ISSN: 1098-1128 ISO Abbreviation: Med Res Rev Publication Date: 2012 Jul |
Date Detail:
|
Created Date: 2012-07-10 Completed Date: 2012-11-09 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 8103150 Medline TA: Med Res Rev Country: United States |
Other Details:
|
Languages: eng Pagination: 687-726 Citation Subset: IM |
Copyright Information:
|
© 2012 Wiley Periodicals, Inc. |
Affiliation:
|
Department of Medicinal Chemistry, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Anti-Inflammatory Agents / therapeutic use Antineoplastic Agents / therapeutic use Antioxidants / metabolism*, therapeutic use Humans Hypoglycemic Agents / therapeutic use Intracellular Signaling Peptides and Proteins / antagonists & inhibitors, metabolism* NF-E2-Related Factor 2 / antagonists & inhibitors, metabolism* Neuroprotective Agents / therapeutic use Oxidative Stress Response Elements Signal Transduction* |
| Grant Support | |
ID/Acronym/Agency:
|
CA125868/CA/NCI NIH HHS; CA133791/CA/NCI NIH HHS; MH093197/MH/NIMH NIH HHS; R01 CA133791-01A2/CA/NCI NIH HHS; R01 CA133791-02/CA/NCI NIH HHS; R01 CA133791-03/CA/NCI NIH HHS; R03 CA125868-01A1/CA/NCI NIH HHS; R03 CA125868-02/CA/NCI NIH HHS; R03 MH093197-01/MH/NIMH NIH HHS; R03 MH093197-02/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Anti-Inflammatory Agents; 0/Antineoplastic Agents; 0/Antioxidants; 0/Hypoglycemic Agents; 0/Intracellular Signaling Peptides and Proteins; 0/NF-E2-Related Factor 2; 0/Neuroprotective Agents |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Future Developments to Minimize ART Risks.
Next Document: Facile synthesis of anisotropic Au@SiO(2) core-shell nanostructures.