Abstract
Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby regulating the cyclic nucleotide signalling pathways and biological responses. PDEs inhibitors can be used clinically for treatment of several diseases including central nervous system disorders, erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, and inflammatory diseases such as chronic obstructive pulmonary disease. However, the unfavourable risk-benefit ratio and side-effect profiles of non-selective PDEs inhibitors have impeded their therapeutic success and therefore spurred the pharmaceutical industry to develop family-selective PDE inhibitors. Given the recent remarkable advances in structure-based drug design, this review will summarize developments and achievements in structure-based search, design and optimization of PDEs inhibitors, and highlight the challenges that need to be addressed.
Keywords: Crystal structure, Cyclic nucleotide signalling pathway, Family-selective inhibitor, Medicinal chemistry, Phosphodiesterases, Structure-based drug design.
Current Topics in Medicinal Chemistry
Title:Structure-Based Discovery of PDEs Inhibitors
Volume: 16 Issue: 9
Author(s): Li Li, Wuyan Chen, Tiantian Chen, Jing Ren and Yechun Xu
Affiliation:
Keywords: Crystal structure, Cyclic nucleotide signalling pathway, Family-selective inhibitor, Medicinal chemistry, Phosphodiesterases, Structure-based drug design.
Abstract: Phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP, thereby regulating the cyclic nucleotide signalling pathways and biological responses. PDEs inhibitors can be used clinically for treatment of several diseases including central nervous system disorders, erectile dysfunction, pulmonary hypertension, acute refractory cardiac failure, and inflammatory diseases such as chronic obstructive pulmonary disease. However, the unfavourable risk-benefit ratio and side-effect profiles of non-selective PDEs inhibitors have impeded their therapeutic success and therefore spurred the pharmaceutical industry to develop family-selective PDE inhibitors. Given the recent remarkable advances in structure-based drug design, this review will summarize developments and achievements in structure-based search, design and optimization of PDEs inhibitors, and highlight the challenges that need to be addressed.
Export Options
About this article
Cite this article as:
Li Li, Chen Wuyan, Chen Tiantian, Ren Jing and Xu Yechun, Structure-Based Discovery of PDEs Inhibitors, Current Topics in Medicinal Chemistry 2016; 16 (9) . https://dx.doi.org/10.2174/1568026615666150825142134
DOI https://dx.doi.org/10.2174/1568026615666150825142134 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...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
-
Anti-VEGF/VEGFR2 Monoclonal Antibodies and their Combinations with PD-1/PD-L1 Inhibitors in Clinic
Current Cancer Drug Targets Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Current Topics in Medicinal Chemistry Nitric Oxide Synthase Function in Exercise
Current Enzyme Inhibition Atypical Presentation Of Anti-Retroviral Therapy Induced Lactic Acidosis as Acute Right Ventricular Failure And Severe Pulmonary Hypertension
New Emirates Medical Journal Metabolic Syndrome as a Modifier of Atherosclerosis in Murine Models
Current Drug Targets Cerebral Aneurysm Formation in Nitric Oxide Synthase-3 Knockout Mice
Current Neurovascular Research First Comprehensive Analysis of Outcomes in Adult Patients after Percutaneous Closure of Isolated Secundum Atrial Septal Defects
Cardiovascular & Hematological Agents in Medicinal Chemistry Editorial [Hot Topic: Waiting for Action on the Osteoarthritis Front (Guest Editors: Virginia Byers Kraus and Thomas Aigner)]
Current Drug Targets Advanced Glycation End Products (AGEs) and their Involvement in Liver Disease
Current Pharmaceutical Design Strategies to Reduce Oxidative Stress in Glaucoma Patients
Current Neuropharmacology Systemic DNA Damage Response and Metabolic Syndrome as a Premalignant State
Current Molecular Medicine Current Theories and Clinical Trial Evidence for Limiting Human Abdominal Aortic Aneurysm Growth
Current Drug Targets The Malignant Obesity Hypoventilation Syndrome (MOHS)
Current Respiratory Medicine Reviews Chemistry and Pharmacological Properties of Some Natural and Synthetic Antioxidants for Heavy Metal Toxicity
Current Medicinal Chemistry Patent Foramen Ovale, the Role of Antiplatelet Therapy Alone or Anticoagulant Therapy Alone Versus Device Closure for Cryptogenic Stroke: A Review of the Literature and Current Recommendations
Cardiovascular & Hematological Agents in Medicinal Chemistry The VHL Tumor Suppressor: Master Regulator of HIF
Current Pharmaceutical Design The General Practitioners Role in Promoting Physical Activity to Older Adults: A Review Based on Program Theory
Current Aging Science Patent Selections
Recent Patents on Inflammation & Allergy Drug Discovery Nitric Oxide and Oral Diseases: Can We Talk About It?
Cardiovascular & Hematological Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Hypertension Reviews