Abstract
The diacylglycerol-responsive C1 domains of protein kinase C and of the related classes of signaling proteins represent highly attractive targets for drug development. The signaling functions that are regulated by C1 domains are central to cellular control, thereby impacting many pathological conditions. Our understanding of the diacylglycerol signaling pathways provides great confidence in the utility of intervention in these pathways for treatment of cancer and other conditions. Multiple compounds directed at these signaling proteins, including compounds directed at the C1 domains, are currently in clinical trials, providing strong validation for these targets. Extensive understanding of the structure and function of C1 domains, coupled with detailed insights into the molecular details of ligand – C1 domain interactions, provides a solid basis for rational and semi-rational drug design. Finally, the complexity of the factors contributing to ligand – C1 domain interactions affords abundant opportunities for manipulation of selectivity; indeed, substantially selective compounds have already been identified.
Keywords: Protein kinase C, phorbol ester, RasGRP, bryostatin, C1 domain
Current Drug Targets
Title: Wealth of Opportunity - The C1 Domain as a Target for Drug Development
Volume: 9 Issue: 8
Author(s): P. M. Blumberg, N. Kedei, N. E. Lewin, D. Yang, G. Czifra, Y. Pu, M. L. Peach and V .E. Marquez
Affiliation:
Keywords: Protein kinase C, phorbol ester, RasGRP, bryostatin, C1 domain
Abstract: The diacylglycerol-responsive C1 domains of protein kinase C and of the related classes of signaling proteins represent highly attractive targets for drug development. The signaling functions that are regulated by C1 domains are central to cellular control, thereby impacting many pathological conditions. Our understanding of the diacylglycerol signaling pathways provides great confidence in the utility of intervention in these pathways for treatment of cancer and other conditions. Multiple compounds directed at these signaling proteins, including compounds directed at the C1 domains, are currently in clinical trials, providing strong validation for these targets. Extensive understanding of the structure and function of C1 domains, coupled with detailed insights into the molecular details of ligand – C1 domain interactions, provides a solid basis for rational and semi-rational drug design. Finally, the complexity of the factors contributing to ligand – C1 domain interactions affords abundant opportunities for manipulation of selectivity; indeed, substantially selective compounds have already been identified.
Export Options
About this article
Cite this article as:
Blumberg M. P., Kedei N., Lewin E. N., Yang D., Czifra G., Pu Y., Peach L. M. and Marquez .E. V, Wealth of Opportunity - The C1 Domain as a Target for Drug Development, Current Drug Targets 2008; 9 (8) . https://dx.doi.org/10.2174/138945008785132376
DOI https://dx.doi.org/10.2174/138945008785132376 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
- 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
-
Statins as Either Immunomodulators or Anti-Cancer Drugs: Functional Activities on Tumor Stromal Cells and Natural Killer Cells
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Novel Therapeutic Strategies Against Cancer: Marine-derived Drugs May Be the Answer?
Anti-Cancer Agents in Medicinal Chemistry Cannabis sativa L. Constituents and Their Role in Neuroinflammation
Current Bioactive Compounds Na+-H+ Exchanger, pH Regulation and Cancer
Recent Patents on Anti-Cancer Drug Discovery Antitumor Activities of Interleukin-27 on Melanoma
Endocrine, Metabolic & Immune Disorders - Drug Targets Threes Company: Regulation of Cell Fate by Statins
Current Drug Targets - Cardiovascular & Hematological Disorders Recent Progress in the Development of Fluorometric Chemosensors to Detect Enzymatic Activity
Current Medicinal Chemistry Genomic Organization and Control of the Grb7 Gene Family
Current Genomics Cannabinoids, Immune System and Cytokine Network
Current Pharmaceutical Design Long Non-Coding RNAs As Epigenetic Regulators in Cancer
Current Pharmaceutical Design In-Vitro Antiproliferative Activity of New Tetrahydroisoquinolines (THIQs) on Ishikawa Cells and their 3D Pharmacophore Models
Letters in Drug Design & Discovery From the Table to the Bedside: Can Food-Derived Sulforaphane be used as a Novel Agent to Treat Leukemia?
Current Cancer Drug Targets Functions of S100 Proteins
Current Molecular Medicine Multiple Biological Activities of Lactic Acid in Cancer: Influences on Tumor Growth,Angiogenesis and Metastasis
Current Pharmaceutical Design Current Status and Perspectives in Ceramide-Targeting Molecular Medicine
Current Pharmaceutical Design The Multiple Pharmaceutical Potential of Curcumin in Parkinson's Disease
CNS & Neurological Disorders - Drug Targets The Role of Oxidative Stress in Smoking-Related Diseases
Mini-Reviews in Organic Chemistry Targeted Therapies in Lung Cancers: Current Landscape and Future Prospects
Recent Patents on Anti-Cancer Drug Discovery The Emerging Role of Vascular Endothelial Growth Factor (VEGF) in Vascular Homeostasis: Lessons from Recent Trials with Anti-VEGF Drugs
Current Vascular Pharmacology SOCS6 Functions as a Tumor Suppressor by Inducing Apoptosis and Inhibiting Angiogenesis in Human Prostate Cancer
Current Cancer Drug Targets