Document Detail

MEK inhibitors: a therapeutic approach to targeting the Ras-MAP kinase pathway in tumors.
MedLine Citation:
PMID:  15180527     Owner:  NLM     Status:  MEDLINE    
The Ras-Raf-MEK-ERK intracellular signaling cascade can be activated in response to a variety of extracellular stimuli. Growth factor binding to extracellular receptors results in activation of Ras, which in turn interacts with and activates Raf, leading to the phosphorylation of the dual specificity kinase MEK (MAP kinase kinase) on two distinct serine residues. MEK possesses a number of unique biochemical and biological features that make it an attractive target from an anticancer drug development perspective. The identification and subsequent testing of highly selective small molecule inhibitors of MEK have served to re-enforce the long held belief that the MEK/ERK module plays a critical role in controlling a number of cellular events that are critical to tumor cell growth and survival. We have witnessed advancement of the first MEK-targeted clinical drug candidate into clinical trials with the entry of CI-1040. The evaluation of sufficiently potent and selective MEK inhibitors in well-designed clinical trials is critical for ultimate validation of MEK as a molecular-based anticancer drug target.
Judith S Sebolt-Leopold
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current pharmaceutical design     Volume:  10     ISSN:  1381-6128     ISO Abbreviation:  Curr. Pharm. Des.     Publication Date:  2004  
Date Detail:
Created Date:  2004-06-07     Completed Date:  2004-07-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1907-14     Citation Subset:  IM    
Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48103, USA.
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MeSH Terms
Drug Delivery Systems / methods*
Enzyme Inhibitors / pharmacology*
MAP Kinase Kinase Kinases / antagonists & inhibitors*,  metabolism
MAP Kinase Signaling System / drug effects*,  physiology
Neoplasms / drug therapy*,  enzymology
ras Proteins / antagonists & inhibitors,  metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; EC Kinase Kinase Kinases; EC Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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