Abstract
Phosphoinositide 3-kinases (PI3K) represent a family of intracellular signaling proteins, which control a variety of important cellular functions such as proliferation, apoptosis and migration. Recent findings suggest an involvement of PI3K in the pathogenesis of numerous diseases including cancer, heart failure and autoimmune / inflammatory disorders. This review summarizes the current knowledge of the emerging therapeutic value of PI3K as targets for the intervention of several pathological disorders and in particular focusing on oncogenesis. A brief introduction on the molecular and biochemical features of these signaling proteins will be followed by a depiction of signaling interactions of PI3K in a cellular context. PI3K dependent signaling involved in the control of cell growth, proliferation, survival and cytoskeletal remodeling and the link to cellular dysfunctions will be discussed. Further we will summarize the phenotypic consequences by genetic targeting PI3K signaling in mice. In its final part this review outlines challenges and activities considering PI3K as targets for therapeutic intervention and progress in the development of first generation small molecule inhibitors.
Keywords: pI 3-kinase, target, inhibitor, signal transduction, cancer, inflammation
Current Pharmaceutical Design
Title: Phosphoinositide 3-Kinases as Targets for Therapeutic Intervention
Volume: 10 Issue: 16
Author(s): Reinhard Wetzker and Christian Rommel
Affiliation:
Keywords: pI 3-kinase, target, inhibitor, signal transduction, cancer, inflammation
Abstract: Phosphoinositide 3-kinases (PI3K) represent a family of intracellular signaling proteins, which control a variety of important cellular functions such as proliferation, apoptosis and migration. Recent findings suggest an involvement of PI3K in the pathogenesis of numerous diseases including cancer, heart failure and autoimmune / inflammatory disorders. This review summarizes the current knowledge of the emerging therapeutic value of PI3K as targets for the intervention of several pathological disorders and in particular focusing on oncogenesis. A brief introduction on the molecular and biochemical features of these signaling proteins will be followed by a depiction of signaling interactions of PI3K in a cellular context. PI3K dependent signaling involved in the control of cell growth, proliferation, survival and cytoskeletal remodeling and the link to cellular dysfunctions will be discussed. Further we will summarize the phenotypic consequences by genetic targeting PI3K signaling in mice. In its final part this review outlines challenges and activities considering PI3K as targets for therapeutic intervention and progress in the development of first generation small molecule inhibitors.
Export Options
About this article
Cite this article as:
Wetzker Reinhard and Rommel Christian, Phosphoinositide 3-Kinases as Targets for Therapeutic Intervention, Current Pharmaceutical Design 2004; 10 (16) . https://dx.doi.org/10.2174/1381612043384402
DOI https://dx.doi.org/10.2174/1381612043384402 |
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
-
Calcium Homeostasis and Kinetics in Heart Failure
Medicinal Chemistry A Review of the Pharmacological Properties of 3,4-dihydro-2(1H)- quinolinones
Mini-Reviews in Medicinal Chemistry Radial Distribution of Elasticity in Porcine Thoracic Aorta
Vascular Disease Prevention (Discontinued) Alzheimers Disease and n-3 Polyunsaturated Fatty Acids: Beneficial Effects and Possible Molecular Pathways Involved
Current Signal Transduction Therapy Transactivation of ErbB Receptors by Leptin in the Cardiovascular System: Mechanisms, Consequences and Target for Therapy
Current Pharmaceutical Design Acute Antithrombotic Treatment of Ischemic Stroke
Current Vascular Pharmacology Pathophysiology of Idiopathic Atrial Fibrillation - Prognostic and Treatment Implications
Current Pharmaceutical Design Novel Applications for Invasive and Non-invasive Tools in the Era of Contemporary Percutaneous Coronary Revascularisation
Current Cardiology Reviews Role of Gut Microbiota in Human Health and Diseases
Current Nutrition & Food Science Quality, not Quantity: The Role of Natural Products and Chemical Proteomics in Modern Drug Discovery
Combinatorial Chemistry & High Throughput Screening Oxidative Stress & FoxO Transcription Factors in Cardiovascular Aging
Current Medicinal Chemistry PARADIGM - HF: The Rise of the Arnis
Reviews on Recent Clinical Trials Melatonin and Hypothalamic-Pituitary-Gonadal Axis
Current Medicinal Chemistry Anti-Apoptotic Effect of Human Telomerase Reverse Transcriptase on Endothelial Cells under Oxidative Stress, Independent of Telomere Elongation and Telomerase Activity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Inflammatory Mechanisms in Atherosclerosis: The Impact of Matrix Metalloproteinases
Current Topics in Medicinal Chemistry Interrupting the Natural History of Diabetes Mellitus: Lifestyle, Pharmacological and Surgical Strategies Targeting Disease Progression
Current Vascular Pharmacology Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms
Anti-Cancer Agents in Medicinal Chemistry High-Density Lipoprotein and Low-Density Lipoprotein Subfractions in Patients with Chronic Kidney Disease
Current Vascular Pharmacology Leishmaniasis: Current Treatment and Prospects for New Drugs and Vaccines
Current Medicinal Chemistry Renovascular Hypertension: Lesion Detection, Patient Selection, Treatment Options and Results
Current Hypertension Reviews