Abstract
CNS drug development is characterized by an especially high attrition rate, despite clear unmet medical needs in the field of neuro-pharmacology and significant investment in R&D of novel CNS drug treatments. Here, we overview the issues underlying the intrinsic difficulty of CNS drugs development, including obstacles of pharmacokinetic nature and lack of predictivity of preclinical tests. We highlight current efforts to overcome these limitations, with an emphasis on modeling opportunities towards early recognition of CNS candidates (stressing the possibilities of multi-target directed ligands or “magic shotguns”) and different approaches to improve CNS bioavailability.
Keywords: ADMET models, biomarkers, CNS drugs, in vitro models, in silico models, multi-target directed ligands.
Mini-Reviews in Medicinal Chemistry
Title:CNS Drug Development – Lost in Translation?
Volume: 12 Issue: 10
Author(s): A. Talevi, C. L. Bellera, M. Di Ianni, M. Gantner, L. E. Bruno-Blanch and . A. Castro
Affiliation:
Keywords: ADMET models, biomarkers, CNS drugs, in vitro models, in silico models, multi-target directed ligands.
Abstract: CNS drug development is characterized by an especially high attrition rate, despite clear unmet medical needs in the field of neuro-pharmacology and significant investment in R&D of novel CNS drug treatments. Here, we overview the issues underlying the intrinsic difficulty of CNS drugs development, including obstacles of pharmacokinetic nature and lack of predictivity of preclinical tests. We highlight current efforts to overcome these limitations, with an emphasis on modeling opportunities towards early recognition of CNS candidates (stressing the possibilities of multi-target directed ligands or “magic shotguns”) and different approaches to improve CNS bioavailability.
Export Options
About this article
Cite this article as:
Talevi A., Bellera L. C., Ianni Di M., Gantner M., Bruno-Blanch E. L. and Castro A. ., CNS Drug Development – Lost in Translation?, Mini-Reviews in Medicinal Chemistry 2012; 12 (10) . https://dx.doi.org/10.2174/138955712802762356
DOI https://dx.doi.org/10.2174/138955712802762356 |
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
-
MicroRNAs in Leukemias: Emerging Diagnostic Tools and Therapeutic Targets
Current Drug Targets Recent Developments in the Chemical Biology of Epothilones
Current Pharmaceutical Design Involvement of L-Carnitine in Cellular Metabolism: Beyond Acyl-CoA Transport
Mini-Reviews in Medicinal Chemistry Targeting Monoamine Oxidases with Multipotent Ligands: An Emerging Strategy in the Search of New Drugs Against Neurodegenerative Diseases
Current Medicinal Chemistry Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism Prion Disease: Chemotherapeutic Strategies
Infectious Disorders - Drug Targets Nanoparticles vs Cancer: A Multifuncional Tool
Current Topics in Medicinal Chemistry New Spirocyclic Hydroxamic Acids as Effective Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Protein Amyloidogenesis Investigated by Small Angle Scattering
Current Pharmaceutical Design Indoleamine 2,3-Dioxygenase in Immune Suppression and Cancer
Current Cancer Drug Targets 7-aa Peptide Mimic from HVR1 of HCV Protects Hepatic Injury in Rats by Reduced Expression of Key Pro-Inflammatory Factors
Inflammation & Allergy - Drug Targets (Discontinued) Anti-Seizure Medications and Estradiol for Neuroprotection in Epilepsy: The 2013 Update
Recent Patents on CNS Drug Discovery (Discontinued) Vitamins B1, B2, B3 and B9 – Occurrence, Biosynthesis Pathways and Functions in Human Nutrition
Mini-Reviews in Medicinal Chemistry Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease
Current Alzheimer Research Exploring the Multifunctional Neuroprotective Promise of Rasagiline Derivatives for Multi-Dysfunctional Alzheimer’s Disease
Current Pharmaceutical Design Metallothionein as a Scavenger of Free Radicals - New Cardioprotective Therapeutic Agent or Initiator of Tumor Chemoresistance?
Current Drug Targets “SLY AS A FOXO”: New Paths with Forkhead Signaling in the Brain
Current Neurovascular Research A Review of Titanium Di Oxide Nanoparticles - Synthesis, Applications and Toxicity Concerns
Nanoscience & Nanotechnology-Asia Therapeutic Application of Histone Deacetylase Inhibitors for Stroke
Central Nervous System Agents in Medicinal Chemistry Delineating Characteristic Sequence and Structural Features of Precursor and Mature Piwi-interacting RNAs of Epithelial Ovarian Cancer
Current Bioinformatics