Skip to main content

RAS/RAF/MEK Inhibitors in Oncology

Buy Article:

$63.00 plus tax (Refund Policy)

Abstract:

The RAS/RAF/MEK signaling pathway plays a central role in mediating both proliferation and survival of cancer cells. These proteins are a group of serine/threonine kinases activated in response to a variety of extracellular stimuli and mediate signal transduction from the cell surface towards both nuclear and cytosolic targets. In combination with several other signaling pathways, they can differentially alter phosphorylation status of the transcription factors. A controlled regulation of these cascades is involved in cell proliferation and differentiation, whereas an unregulated activation of these kinases can result in oncogenesis.

Dysregulation of the RAS/RAF/MEK pathway has been detected in more than 30% of human tumors, however mutations in the MEK1 and MEK2 genes are seldom, so that hyperactivation of MEK1/2 usually results from gain-of-function mutations in RAS and/or B-RAF.

In addition, alteration of the pathways is often associated with drug resistance in the clinic, such as the case of K-RAS mutant expressing tumors.

Since RAS protein is a difficult target, alternative ways altering post-translational modifications using farnesyl transferase inhibitors have been adopted. Drug discovery programs have therefore largely focused on B-RAF and MEK.

In this review we will discuss the most promising strategies developed to target these kinases and the most recent inhibitors facing the preclinical and clinical setting, also considering their structure-activity relationship (SAR).

Keywords: ATP competitive; ATP non; ATP non competitive; MAPK inhibitors; MEK; RAF; allosteric inhibitors; competitive; intracellular signalling; kinases; mutant B-RAF; small molecule inhibitors

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986712799320510

Publication date: March 1, 2012

More about this publication?
  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
ben/cmc/2012/00000019/00000008/art00008
dcterms_title,dcterms_description,pub_keyword
6
5
20
40
5

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more