E6201 [(3S,4R,5Z,8S,9S,11E)-14-(Ethylamino)-8, 9,16-trihydroxy-3,4-dimethyl-3,4,9,19-tetrahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione], a Novel Kinase Inhibitor of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase (MEK)-1 and MEK Kinase-1: In Vitro Characterization of Its Anti-Inflammatory and Antihyperproliferative Activities

2009 ◽  
Vol 331 (2) ◽  
pp. 485-495 ◽  
Author(s):  
Masaki Goto ◽  
Jesse Chow ◽  
Kenzo Muramoto ◽  
Ken-ichi Chiba ◽  
Satoshi Yamamoto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kinase Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Signal Regulated Kinase ◽  
In Vitro Characterization ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 776-783 ◽  
Author(s):  
Matthew J. Sale ◽  
Simon J. Cook
Keyword(s):  
Protein Kinase ◽  
Present Article ◽  
Acquired Resistance ◽  
Mitogen Activated Protein Kinase ◽  
Inhibitor Activity ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Signalling Cascade

Recent clinical data with BRAF and MEK1/2 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 1/2] inhibitors have demonstrated the remarkable potential of targeting the RAF–MEK1/2–ERK1/2 signalling cascade for the treatment of certain cancers. Despite these advances, however, only a subset of patients respond to these agents in the first instance, and, of those that do, acquired resistance invariably develops after several months. Studies in vitro have identified various mechanisms that can underpin intrinsic and acquired resistance to MEK1/2 inhibitors, and these frequently recapitulate those observed clinically. In the present article, we review these mechanisms and also discuss recent advances in our understanding of how MEK1/2 inhibitor activity is influenced by pathway feedback.

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