title: Recent developments in anti-cancer agents targeting the Ras/Raf/ MEK/ERK pathway.
abstract: The Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) pathway mediates cellular responses to different growth signals and is frequently deregulated in cancer. There are three Raf kinases-A-Raf, B-Raf, and C-Raf; however, only B-Raf is frequently mutated in various cancers. The most common B-Raf mutation involves a substitution of a glutamic acid residue to a valine moiety at codon 600. Subsequently, the MAPK pathway is constitutively activated, even in the absence of any growth signals. Although early attempts to target Ras have not yielded any viable drug candidates, many novel compounds inhibiting the activities of Raf and MEK have been developed and investigated in clinical trials in recent years. The first MEK inhibitor (CI-1040) lacked efficacy in clinical trials, but its low toxicity has encouraged the search for novel compounds with enhanced target potency to inhibit MAPK activation at low nanomolar concentrations. In this review, we will discuss new patents or patent applications related to inhibitors of the Ras/Raf/MEK/ERK pathway.
authors.affiliation: Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, TX 77030, USA. kkwong@mdanderson.org
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D048490:raf Kinases / Q000037:antagonists & inhibitors*; D018631:ras Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D048493:Proto-Oncogene Proteins B-raf; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D018631:ras Proteins