Abstract
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.
Keywords: mek1, mek, mek Inhibitor, map kinase, erk, cI-1040, tumor
Current Pharmaceutical Design
Title: MEK Inhibitors: A Therapeutic Approach to Targeting the Ras-MAP Kinase Pathway in Tumors
Volume: 10 Issue: 16
Author(s): Judith S. Sebolt-Leopold
Affiliation:
Keywords: mek1, mek, mek Inhibitor, map kinase, erk, cI-1040, tumor
Abstract: 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.
Export Options
About this article
Cite this article as:
Sebolt-Leopold S. Judith, MEK Inhibitors: A Therapeutic Approach to Targeting the Ras-MAP Kinase Pathway in Tumors, Current Pharmaceutical Design 2004; 10 (16) . https://dx.doi.org/10.2174/1381612043384439
DOI https://dx.doi.org/10.2174/1381612043384439 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
αvβ3 Integrin-Targeted Peptide/Peptidomimetic-Drug Conjugates: In-Depth Analysis of the Linker Technology
Current Topics in Medicinal Chemistry Ovarian Cancer Biomarkers: A Focus on Genomic and Proteomic Findings
Current Genomics Molecular Modeling Applied to Anti-Cancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry Use of Kv1.3 Blockers for Inflammatory Skin Conditions
Current Medicinal Chemistry Progress Towards Clinically Useful Aldosterone Synthase Inhibitors
Current Topics in Medicinal Chemistry Effect of PI3K/AKT/mTOR Signaling Pathway on Regulating and Controlling the Anti-Invasion and Metastasis of Hepatoma Cells by Bufalin
Recent Patents on Anti-Cancer Drug Discovery Antioxidant Effect of Mangiferin and its Potential to be a Cancer Chemoprevention Agent
Letters in Drug Design & Discovery Chemical Structure Characteristics and Bioactivity of Small Molecule FAK Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Ectopic Thyroid Gland: Description of a Case and Review of the Literature
Endocrine, Metabolic & Immune Disorders - Drug Targets The Dark Side of Stem Cells: Triggering Cancer Progression by Cell Fusion
Current Molecular Medicine Mitochondrial Therapeutics for Cardioprotection
Current Pharmaceutical Design Tumor Vasculature Targeting Through NGR Peptide-Based Drug Delivery Systems
Current Pharmaceutical Biotechnology Tumor Systems Need to be Rendered Usable for a New Action-Theoretical Abstraction: The Starting Point for Novel Therapeutic Options
Current Cancer Therapy Reviews Comprehensive Review of Cancer Chemopreventive Agents Evaluated in Experimental Carcinogenesis Models and Clinical Trials
Current Medicinal Chemistry Amphiphilic Oligomers: A New Kind of Macromolecular Carrier of Antimitotic Drugs
Current Medicinal Chemistry - Anti-Cancer Agents Applications of the Rare Earth Elements in Cancer Imaging and Therapy
Current Nanoscience Pharmacological Inhibition of the Bcl-2 Family of Apoptosis Regulators as Cancer Therapy
Current Molecular Pharmacology Xenobiotic-Metabolizing Enzymes in Human Lung
Current Drug Metabolism Role of ABC Transporters in Veterinary Medicine: Pharmaco- Toxicological Implications
Current Medicinal Chemistry Current Targeting Strategies for Adenovirus Vectors in Cancer Gene Therapy
Current Cancer Drug Targets