ReviewMolecules (Basel, Switzerland)2024
Experimental and Computational Methods to Assess Central Nervous System Penetration of Small Molecules.
Review in Molecules (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Penetrating potential evaluation of cyclotriphosphazenes target blood-brain barrier via computational toxicology methods.iScience · 2026Article
- Design, preclinical evaluation, and multicenter phase 1 clinical study of HZ-A-018 for relapsed or refractory central nervous system lymphoma.Acta pharmaceutica Sinica. B · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- 4-methylbenzyl 5-arylthiophene-2-carboxylates as Multitarget Directed Ligands Scaffolds (MTDLs): Synthesis, in-silico docking studies, and evaluation of dual selective enzymatic inhibition (AChE & MAO-B).Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Metabolic reprogramming in sepsis-associated encephalopathy: emerging mechanisms, candidate biomarkers, and future therapeutic directions.Frontiers in medicine · 2026Review
- Therapeutic Approaches Interfering with Nuclear Localization Signals: An Emerging Strategy for CNS-Related Diseases.Current neuropharmacology · 2026Review
- Traditional Chinese Medicine and Ferroptosis in Alzheimer's Disease: A Potential Therapeutic Approach.Drug design, development and therapy · 2026Review
- A surrogate barrier model for high-throughput blood-brain barrier permeability prediction: integrating LLC-PK1-MOCK/MDR1 Cells and lysosomal trapping correction.Drug delivery · 2025Article
- Unraveling the Antihyperglycemic Effects of Dipeptyl Peptidase-4 Inhibitors in Rodents: A Multi-Faceted Approach Combining Effects on Glucose Homeostasis, Molecular Docking, and ADMET Profiling.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Prodrug Approach as a Strategy to Enhance Drug Permeability.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Neurotherapeutics across blood-brain barrier: screening of BBB-permeable and CNS-active molecules for neurodegenerative disease.Frontiers in pharmacology · 2025Article
- Discovery of F-18 labeled repurposed CNS drugs by computational strategy for effective tau imaging and alzheimer's diagnosis.PloS one · 2025Article
- Article
- Log BB Prediction Models Using TLC and HPLC Retention Values as Protein Affinity Data.Pharmaceutics · 2024Article
- Applicability of MDR1 Overexpressing Abcb1KO-MDCKII Cell Lines for Investigating In Vitro Species Differences and Brain Penetration Prediction.Pharmaceutics · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In CNS drug discovery, the estimation of brain exposure to lead compounds is critical for their optimization. Compounds need to cross the blood-brain barrier (BBB) to reach the pharmacological targets in the CNS. The BBB is a complex system involving passive and active mechanisms of transport and efflux transporters such as P-glycoproteins (P-gp) and breast cancer resistance protein (BCRP), which play an essential role in CNS penetration of small molecules. Several in vivo, in vitro, and in silico methods are available to estimate human brain penetration. Preclinical species are used as in vivo models to understand unbound brain exposure by deriving the Kp,uu parameter and the brain/plasma ratio of exposure corrected with the plasma and brain free fraction. The MDCK-mdr1 (Madin Darby canine kidney cells transfected with the MDR1 gene encoding for the human P-gp) assay is the commonly used in vitro assay to estimate compound permeability and human efflux. The in silico methods to predict brain exposure, such as CNS MPO, CNS BBB scores, and various machine learning models, help save costs and speed up compound discovery and optimization at all stages. These methods enable the screening of virtual compounds, building of a CNS penetrable compounds library, and optimization of lead molecules for CNS penetration. Therefore, it is crucial to understand the reliability and ability of these methods to predict CNS penetration. We review the in silico, in vitro, and in vivo data and their correlation with each other, as well as assess published experimental and computational approaches to predict the BBB penetrability of compounds.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.