ReviewNature reviews. Drug discovery2021
Ligand binding at the protein-lipid interface: strategic considerations for drug design.
Review in Nature reviews. Drug discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 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
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Ion Selectivity in the ENaC/DEG Family: A Systematic Review with Supporting Analysis.International journal of molecular sciences · 2021Pooled it
- Probing non-covalent membrane protein-lipid interactions using sheath liquid capillary electrophoresis-native top-down mass spectrometry.The Analyst · 2026Article
- Docking-score landscapes shape active-learning performance across Vina, Glide, and SILCS.Journal of computer-aided molecular design · 2026Article
- Targeting the Protein-Membrane Interface Enables Design of Long-Acting CFTR Potentiators.ACS chemical biology · 2026Article
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.Journal of medicinal chemistry · 2026Article
- Open-Source Molecular Docking and AI-Augmented Structure-Based Drug Design: Current Workflows, Challenges, and Opportunities.International journal of molecular sciences · 2026Review
- Structures of respiratory supercomplexes and ATP synthase oligomers in mammalian mitochondrial inner membrane.Nature communications · 2026Article
- Quantification of Ligand-Membrane Interactions Using DNP-NMR Relaxometry.Analytical chemistry · 2026Article
- Polypharmacology of anthelmintics at host and parasite ion channels.PLoS pathogens · 2026Article
- Unveiling the Bio-Interface via Spectroscopic and Computational Studies of (Propyl-3-ol/butyl-4-ol)triphenyltin(IV) Compound Binding to Human Serum Transferrin.Materials (Basel, Switzerland) · 2026Article
- Lipid Dependence of CYP3A4 Activity in Nanodiscs.Biology · 2026Article
- Characterization of Cell-Surface Interactions of Ligands UsingAnalytical chemistry · 2026Article
- Optimization and Characterization of SHIP1 Ligands for Cellular Target Engagement and Activity in Alzheimer's Disease Models.bioRxiv : the preprint server for biology · 2026Article
- Exploring Lipid Metabolic Reprogramming: Mechanistic Insights and Implications for Tumor Radiotherapy.International journal of biological sciences · 2026Review
- Structural and allosteric effects of the membrane-bound PI3Kα H1047R mutation and opportunities for drug discovery.Communications chemistry · 2025Article
- Evaluation of Small-Molecule Binding Site Prediction Methods on Membrane-Embedded Protein Interfaces.Journal of chemical information and modeling · 2025Article
- Phytochemical Analysis and Compound Profiling ofAnalytical science advances · 2025Article
- The Fe-Cyclam-Derived Compound [Fe(cyclam)sal]PFACS omega · 2025Article
- A quantitative analysis of ligand binding at the protein-lipid bilayer interface.Communications chemistry · 2025Article
- The Influence of Phosphoinositide Lipids in the Molecular Biology of Membrane Proteins: Recent Insights from Simulations.Journal of molecular biology · 2025Review
1 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
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many drug targets are embedded within the phospholipid bilayer of cellular membranes, including G protein-coupled receptors, ion channels, transporters and membrane-bound enzymes. Increasing evidence from biophysical and structural studies suggests that many small-molecule drugs commonly associate with these targets at binding sites at the protein-phospholipid interface. Without a direct path from bulk solvent to a binding site, a drug must first partition in the phospholipid membrane before interacting with the protein target. This membrane access mechanism necessarily affects the interpretation of potency data, structure-activity relationships, pharmacokinetics and physicochemical properties for drugs that target these sites. With an increasing number of small-molecule intramembrane binding sites revealed through X-ray crystallography and cryogenic electron microscopy, we suggest that ligand-lipid interactions likely play a larger role in small-molecule drug action than commonly appreciated. This Perspective introduces key concepts and drug design considerations to aid discovery teams operating within this target space, and discusses challenges and future opportunities in the field.
Indexed as
Identifiers
What 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.