ReviewNature reviews. Drug discovery2010
The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery.
Review in Nature reviews. Drug discovery, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 281 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
281 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Considerations and recommendations for assessment of plasma protein binding and drug-drug interactions for siRNA therapeutics.Nucleic acids research · 2022Pooled it
- Pharmacokinetics of Dalbavancin in Complicated Staphylococcus aureus Bacteremia: A Secondary Analysis of the DOTS Randomized Clinical Trial.JAMA network open · 2026Trial
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Association between clozapine-induced hypertriglyceridemia and defenestration of liver sinusoidal endothelial cells.Translational psychiatry · 2026Article
- Chalcones as a Versatile Antiviral Scaffold: Molecular Targets, ADMET Profiles, and Translational Challenges.Viruses · 2026Review
- A Multidimensional Evaluation of Sakuranetin againstACS omega · 2026Article
- Deep learning-enabled discovery of antibiotics effective againstScience translational medicine · 2026Article
- Quantitative Competition Binding of Fluorinated Ligands by Real-TimeMagnetic resonance in chemistry : MRC · 2026Article
- Intestinal Organoid-Based Mathematical Modeling Predicts Clinical Gastrointestinal Toxicity of Oral Oncology Drugs.CPT: pharmacometrics & systems pharmacology · 2026Article
- Multianalytical and Theoretical Tendency for the Clarification of the Binding of Lansoprazole and Albumin Protein.ACS omega · 2026Article
- Liquid-Phase Peptide Synthesis of Tropolone-Peptide Hybrid Antimalarials.Organic letters · 2026Article
- Misconceptions among medicinal chemists regarding ADME and PK optimization.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Multiparameter Optimization ofJournal of medicinal chemistry · 2026Article
- Biological Activity and Structural Biology of Current KAT6A Inhibitor Chemotypes.Journal of medicinal chemistry · 2026Article
- Ex vivo drug sensitivity profiling to complement molecular profiling in pediatric precision oncology.NPJ precision oncology · 2026Article
- Physiologically based pharmacokinetic modeling of tafenoquine and evaluation of transporter-mediated drug-drug interactions.Frontiers in pharmacology · 2026Article
- Tissue-autonomous pharmacological direction: how target expression landscapes convert balanced compounds into tissue-selective agents.Frontiers in pharmacology · 2026Article
- Linking biomimetic binding measurements to pharmacokinetic models of volume of distribution and hepatic clearance.ADMET & DMPK · 2026Review
- A Novel Quinolone JH62 (E-2-(Tridec-4-en-1-yl)-quinolin-4(1H)-one) fromMicroorganisms · 2025Article
- Development of Prediction Capabilities for High-Throughput Screening of Physiochemical Properties by Biomimetic Chromatography.Molecules (Basel, Switzerland) · 2025Review
221 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Data from in vitro plasma protein binding experiments that determine the fraction of protein-bound drug are frequently used in drug discovery to guide structure design and to prioritize compounds for in vivo studies. However, we consider that these practices are usually misleading, because in vivo efficacy is determined by the free (unbound) drug concentration surrounding the therapeutic target, not by the free drug fraction. These practices yield no enhancement of the in vivo free drug concentration. So, decisions based on free drug fraction could result in the wrong compounds being advanced through drug discovery programmes. This Perspective provides guidance on the application of plasma protein binding information in drug discovery.
Indexed as
Identifiers
21119731What OpenQuestion holds
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.