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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Hypothalamic mTOR: The Rookie Energy Sensor
Current Molecular Medicine Editorial (Thematic Issue: The Coronary Collateral Circulation – Past, Present and Future)
Current Cardiology Reviews The Anti-Atherogenic Effects of Thiazolidinediones
Current Diabetes Reviews Cardiovascular Effects of Hypoglycemic Agents in Diabetes Mellitus
Current Drug Safety Cerebral White Matter Lesions, Risk of Stroke and Cerebrovascular Protection with Angiotensin Receptor Blockers
Current Drug Therapy Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry Does Angiotensin Converting Enzyme Inhibitor Protect the Heart in Cardiac Surgery? From Laboratory to Operating Room: Clinical Application of Experimental Study
Current Pharmaceutical Design “Seeing is Believing”: Perspectives of Applying Imaging Technology in Discovery Toxicology
Combinatorial Chemistry & High Throughput Screening The Entirely Subcutaneous Defibrillator (S-Icd): State of the Art and Selection of the Ideal Candidate
Current Cardiology Reviews Nephrotoxicity of Bisphenol A (BPA) -An Updated Review
Current Molecular Pharmacology Obesity and Cardioprotection
Current Medicinal Chemistry Oxidative-Nitrosative Stress as a Contributing Factor to Cardiovascular Disease in Subjects with Diabetes
Current Vascular Pharmacology Molecular and Cellular Mechanisms in the Pathophysiology of Severe Head Injury
Current Pharmaceutical Design Common Variants for Heart Failure
Current Genomics Aldose Reductase in Diabetic Microvascular Complications
Current Drug Targets Topoisomerase Enzymes as Therapeutic Targets for Cancer Chemotherapy
Medicinal Chemistry Novel Genetic and Peptide-Based Strategies Targeting the Bcl-2 Family, an Update
Recent Patents on DNA & Gene Sequences Renin Angiotensin System as a Regulator of Cell Volume. Implications to Myocardial Ischemia
Current Cardiology Reviews Innovations in siRNA Research: A Technology Comes of Age
Recent Patents on Anti-Infective Drug Discovery Targeted Therapy of Breast Cancer
Current Pharmaceutical Design