Abstract
Directly inhibiting oncogenic RAS proteins has proven to be an arduous task, as after more than thirty years of intensive investigation, no clinically relevant therapies exist. Recently, two classes of selective small molecule inhibitors that target a cysteine-containing RAS mutant have been developed, representing the first directed approaches to specifically inhibit an oncogenic KRAS mutant. In this mini-review, we first assess the development and targeting strategies associated with novel cysteine-directed RAS inhibitors. Next, we describe the variable oncogenic potency of the KRAS G12C mutant when compared to other KRAS G12 mutants. Lastly, we evaluate how the redox properties of KRAS G12C may play a role in differential signaling and tumorigenic potency of the oncogene, the efficacy of small molecules targeting this specific RAS mutant and further development of directed oncogenic RAS inhibitors.
Keywords: KRAS G12C, RAS inhibition, cysteine-directed inhibitors, RAS oxidation, tethering.
Mini-Reviews in Medicinal Chemistry
Title:Getting a Handle on RAS-targeted Therapies: Cysteine Directed Inhibitors
Volume: 16 Issue: 5
Author(s): Minh V. Huynh and Sharon L. Campbell
Affiliation:
Keywords: KRAS G12C, RAS inhibition, cysteine-directed inhibitors, RAS oxidation, tethering.
Abstract: Directly inhibiting oncogenic RAS proteins has proven to be an arduous task, as after more than thirty years of intensive investigation, no clinically relevant therapies exist. Recently, two classes of selective small molecule inhibitors that target a cysteine-containing RAS mutant have been developed, representing the first directed approaches to specifically inhibit an oncogenic KRAS mutant. In this mini-review, we first assess the development and targeting strategies associated with novel cysteine-directed RAS inhibitors. Next, we describe the variable oncogenic potency of the KRAS G12C mutant when compared to other KRAS G12 mutants. Lastly, we evaluate how the redox properties of KRAS G12C may play a role in differential signaling and tumorigenic potency of the oncogene, the efficacy of small molecules targeting this specific RAS mutant and further development of directed oncogenic RAS inhibitors.
Export Options
About this article
Cite this article as:
Huynh V. Minh and Campbell L. Sharon, Getting a Handle on RAS-targeted Therapies: Cysteine Directed Inhibitors, Mini-Reviews in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1389557515666151001154352
DOI https://dx.doi.org/10.2174/1389557515666151001154352 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- 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
Related Articles
-
Validation of Self-Report of Chest X-Ray Exam at a Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial Center
Reviews on Recent Clinical Trials Anticancer Activity of Ocimum basilicum and the Effect of Ursolic Acid on the Cytoskeleton of MCF-7 Human Breast Cancer Cells
Letters in Drug Design & Discovery Targeting Hypoxia for Sensitization of Tumors to Radio- and Chemotherapy
Current Cancer Drug Targets Cytotoxicity of Novel Sulfanilamides Towards Sensitive and Multidrugresistant Leukemia Cells
Current Medicinal Chemistry Developing Antitumor Magnetic Hyperthermia: Principles, Materials and Devices
Recent Patents on Anti-Cancer Drug Discovery A Retrospective Study on <i>Gloriosa superba</i> and Its Main Active Constituents
The Natural Products Journal Cox Inhibitors as Potential Chemotherapic Drugs for Mesothelioma
Current Respiratory Medicine Reviews Highlights in Peptide Nanoparticle Carriers Intended to Oral Diseases
Current Topics in Medicinal Chemistry The Role of Chronic Periodontitis in Prevention and Treatment of Head and Neck Cancers
Current Cancer Therapy Reviews Chemistry and Biology of Landomycins, an Expanding Family of Polyketide Natural Products
Mini-Reviews in Medicinal Chemistry Coumarin Derivatives as Anti-inflammatory and Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Triggered Activation and Release of Liposomal Prodrugs and Drugs in Cancer Tissue by Secretory Phospholipase A2
Current Drug Delivery Precursors of Magnetic Resonance Imaging Contrast Agents Based on Cystine-coated Iron-oxide Nanoparticles
Current Physical Chemistry A Constrained Probabilistic Matrix Decomposition Method for Predicting miRNA-disease Associations
Current Bioinformatics WISP1 (CCN4) Autoregulates its Expression and Nuclear Trafficking of β-Catenin during Oxidant Stress with Limited Effects upon Neuronal Autophagy
Current Neurovascular Research World Health Organization Classification of Myelodysplastic Syndromes
Current Pharmaceutical Design Fused Xanthone Derivatives as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry New Antiangiogenetic Therapy Beyond Bevacizumab in the Treatment of Advanced Non Small Cell Lung Cancer
Current Pharmaceutical Design Current Approaches to Diagnostics and Therapies of Chronic Diseases: Focus on Molecular and Cell Biology
Current Pharmaceutical Design Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy
Current Cancer Drug Targets