PMID- 23496222
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130319
LR  - 20140731
IS  - 1746-0441 (Print)
IS  - 1746-0441 (Linking)
VI  - 3
IP  - 7
DP  - 2008 Jul
TI  - New small-molecule inhibitors of mitogen-activated protein kinase kinase.
PG  - 801-17
LID - 10.1517/17460441.3.7.801 [doi]
AB  - BACKGROUND: Overexpression of the Ras/Raf/MEK/ERK (extracellular-signal-regulated 
      kinase) pathway is associated with the formation, progression and survival of 
      tumours and has also been implicated in a diverse range of therapeutic areas such 
      as arthritis, organ transplant rejection, asthma and developmental disorders. One 
      approach to down regulation of this pathway is through the inhibition of 
      mitogen-activated protein kinase kinase 1/2 (MEK1/2). OBJECTIVE: The importance 
      of the mitogen-activated protein kinase (MAPK) pathway, MEK1/2 as a therapeutic 
      target and early MEK1/2 inhibitors is discussed, followed by an overview of 
      recent patent activity in the area. METHODS: The patent literature was searched 
      for inhibitors of MEK1/2 published within the last three years; these results are 
      described. Other relevant publications that provide further insight into the 
      discovery and development of these compounds are also discussed. CONCLUSION: The 
      determination of a crystal structure with inhibitor bound has allowed the design 
      of exquisitely selective and potent inhibitors of MEK1/2. Several allosteric 
      inhibitors have advanced to clinical trial and shown some efficacy in cancer as 
      single agents, but the future application of MEK1/2 inhibitors is likely to be 
      either in combination with other therapies or in disorders which are genetically 
      defined as being dependent on the MAPK pathway.
FAU - Spicer, Julie A
AU  - Spicer JA
AD  - University of Auckland, Faculty of Medical and Health Sciences, Auckland Cancer 
      Society Research Centre, Private Bag 92019, Auckland 1142, New Zealand +64 9 
      3737599, ext. 86149 ; +64 9 3737502 ; j.spicer@auckland.ac.nz.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Expert Opin Drug Discov
JT  - Expert opinion on drug discovery
JID - 101295755
EDAT- 2008/07/01 00:00
MHDA- 2008/07/01 00:01
CRDT- 2013/03/19 06:00
PHST- 2013/03/19 06:00 [entrez]
PHST- 2008/07/01 00:00 [pubmed]
PHST- 2008/07/01 00:01 [medline]
AID - 10.1517/17460441.3.7.801 [doi]
PST - ppublish
SO  - Expert Opin Drug Discov. 2008 Jul;3(7):801-17. doi: 10.1517/17460441.3.7.801.