![conference banner](/images/conference-banner.jpeg)
Abstract
The success rate to achieve clinical approval of drugs developed to treat diseases of the central nervous system (CNS) is the lowest of all disease indications. A large contributor to this poor success rate is failure of small molecules to pass through the blood-brain barrier (BBB), a barrier composed of capillary endothelial cells connected by tight junctions that functions to extrude xenobiotics from the brain. Designing small molecules to be BBB penetrant has been the subject of intensive research and has resulted in a series of guidelines to attain the best possible chances of BBB penetration. This review will analyze the current state of thinking in ranking the importance of various physicochemical properties required to select BBB penetrant molecules, describe model systems to determine BBB penetration, summarize data analysis methods and provide an outlook on further developments in the field.
Keywords: Blood-brain barrier, Drug-likeness, Central Nervous System, Neuropharmacology, Physicochemical Properties, Drug Design.
Current Medicinal Chemistry
Title:Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration
Volume: 23 Issue: 14
Author(s): Paul C. Trippier
Affiliation:
Keywords: Blood-brain barrier, Drug-likeness, Central Nervous System, Neuropharmacology, Physicochemical Properties, Drug Design.
Abstract: The success rate to achieve clinical approval of drugs developed to treat diseases of the central nervous system (CNS) is the lowest of all disease indications. A large contributor to this poor success rate is failure of small molecules to pass through the blood-brain barrier (BBB), a barrier composed of capillary endothelial cells connected by tight junctions that functions to extrude xenobiotics from the brain. Designing small molecules to be BBB penetrant has been the subject of intensive research and has resulted in a series of guidelines to attain the best possible chances of BBB penetration. This review will analyze the current state of thinking in ranking the importance of various physicochemical properties required to select BBB penetrant molecules, describe model systems to determine BBB penetration, summarize data analysis methods and provide an outlook on further developments in the field.
Export Options
About this article
Cite this article as:
C. Trippier Paul, Selecting Good ‘Drug-Like’ Properties to Optimize Small Molecule Blood-Brain Barrier Penetration, Current Medicinal Chemistry 2016; 23 (14) . https://dx.doi.org/10.2174/0929867323666160405112353
DOI https://dx.doi.org/10.2174/0929867323666160405112353 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the Treatment of Chronic Inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
A Hypothesis for Regenerative Therapy for Neuronal Disease: Stem Cells within Artificial Niche
Current Signal Transduction Therapy Molecular Genetics of Early- and Late-Onset Alzheimer’s Disease
Current Gene Therapy Current Pathogenesis of Alzheimer’s Disease and Plants Derived Neuroprotective Phytoconstituents: A Comprehensive Review
Current Psychopharmacology Insight γ-Secretase: Structure, Function, and Role in Alzheimer’s Disease
Current Drug Targets Ketamine: New Indications for an Old Drug
Current Drug Targets Neurofilament Proteins as Prognostic Biomarkers in Neurological Disorders
Current Pharmaceutical Design Redox Active Iron at the Center of Oxidative Stress in Alzheimer Disease
Letters in Drug Design & Discovery Subject Index to Volume 9
Current Pharmaceutical Design Regulation of GABA Neurotransmission by Glutamic Acid Decarboxylase (GAD)
Current Pharmaceutical Design GSTP1 Polymorphisms and their Association with Glutathione Transferase and Peroxidase Activities in Patients with Motor Neuron Disease
CNS & Neurological Disorders - Drug Targets Cell and Gene Therapies for Refractory Epilepsy
Current Neuropharmacology The Unbiased Search of Biomarkers in Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Discovering New Treatments for Alzheimer's Disease by Repurposing Approved Medications
Current Topics in Medicinal Chemistry Programmed Axon Death, Synaptic Dysfunction and the Ubiquitin Proteasome System
Current Drug Targets - CNS & Neurological Disorders Potential of Photobiomodulation to Induce Differentiation of Adipose- Derived Mesenchymal Stem Cells into Neural Cells
Current Stem Cell Research & Therapy An Update on the Application of Nano Phytomedicine as an Emerging Therapeutic Tool for Neurodegenerative Diseases
Current Bioactive Compounds Oxidation of Potassium Channels in Neurodegenerative Diseases: A Mini- Review
CNS & Neurological Disorders - Drug Targets Molecular and Cellular Mechanism of Glutamate Receptors in Relation to Amyotrophic Lateral Sclerosis
Current Drug Targets - CNS & Neurological Disorders Natural Compounds Used as Therapies Targeting to Amyotrophic Lateral Sclerosis
Current Pharmaceutical Biotechnology Lambert-Eaton Myasthenic Syndrome: A Very Rare and Tortuously Exasperating Facet of Pre-Synaptic Disorder of Neuromuscular Junction
Current Immunology Reviews (Discontinued)