ArticleJournal of medicinal chemistry2025
Conformational Dynamics in the Cell Membrane Interactions of Bispecific Targeted Degrader Therapeutics.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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
3 citing papers in PubMed.
- DesignMaster: a multi-conditional diffusion framework for rational PROTAC design.Bioinformatics (Oxford, England) · 2026Article
- Evaluation of Oral PROTAC Guidelines: Efflux Ratio Outweighs Chameleonicity Descriptors.ACS medicinal chemistry letters · 2026Article
- Flexible molecular chameleons: structural adaptability and therapeutic applications.Frontiers in chemistry · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis targeting chimeras (PROTACs) offer vast new therapeutic opportunities, but their physicochemical properties are difficult to combine with optimal cell permeability and exposure at the target sites. We have systematically analyzed a data set of more than 3500 PROTACs to investigate how the choice of ubiquitin E3 ligands, linker design, and global molecular properties can be optimized to achieve the desired cell membrane interactions and ultimately membrane permeability and intracellular exposure. We find that conformational flexibility leads to environment-dependent shielding of polar functions and improved interactions with cell membranes but that at the same time, extended, linear conformations within the membrane are beneficial. Linker composition was a major factor in determining the folding propensity. Collectively, our results suggest that strategies to rationally design linkers and to shield polarity selectively within the protein-of-interest (POI) ligand and/or E3 ligand domains rather than more extensive folding may be beneficial in the design of permeable and effective PROTACs.
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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.