ArticleNature chemical biology2026
Navigating condensate micropolarity to enhance small-molecule drug targeting.
Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed.
- Subcellular photochemistry for precision spatial protein targeting.Nature reviews. Chemistry · 2026Review
- The emerging synergy of experimental and computational approaches for therapeutic modulation of biomolecular condensates.SLAS discovery : advancing life sciences R & D · 2026Review
- Uncovering MYOF as a novel therapeutic target in glioblastoma: mechanistic insights and drug discovery.Cell death discovery · 2026Article
- A tunable aqueous architecture modulates functional output in biomolecular condensates.bioRxiv : the preprint server for biology · 2026Article
- Decoding the tactics for coacervate pedestrian crossing the phospholipid membrane.Chemical science · 2026Review
- Asymmetry in Hydrophobicity Induces Electric Potential in Non-Charged Biomolecular Condensates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Prediction of Small-Molecule Partitioning into Biomolecular Condensates from Simulation.JACS Au · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors.
Funding
Abstract
Many pharmaceutical targets partition into biomolecular condensates, whose microenvironments can significantly influence drug distribution. Nevertheless, it is unclear how drug design principles should adjust for these targets to optimize target engagement. To address this question, we systematically investigated how condensate microenvironments influence drug-targeting efficiency. We found that condensates highlight a notable heterogeneity, with nonpolar-residue-enriched condensates being more hydrophobic and housing more hydrophobic drugs. Furthermore, L1000 dataset analysis revealed a strong positive correlation between inhibitor hydrophobicity and targeting efficiency for phase-separated proteins, represented by estrogen receptor 1 (ESR1) enriched with nonpolar residues. We developed random forest models to predict inhibitor targeting efficiency from molecular properties, with hydrophobicity identified as a key determinant. In cellulo experiments with ESR1 condensates confirmed that both binding affinity and hydrophobicity of inhibitors contribute significantly to potency. These results suggest a new drug design principle for phase-separated proteins by considering condensate micropolarity, potentially leading to drugs with optimal target engagement.
Indexed as
Identifiers
40925983What 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.