ArticleNature communications2022
Small molecules targeting the disordered transactivation domain of the androgen receptor induce the formation of collapsed helical states.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 85 citations in OpenAlex.
- GNPS-assisted identification of bioactive constituents fromRSC advances · 2026Article
- Targeting the intrinsically disordered AR-NTD through a machine learning-based enhanced sampling workflow.Nature communications · 2026Article
- Physics-guided design of intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2026Article
- Tumor-derived branched-chain α-keto acids activate Notch signaling in tumor-associated macrophages to limit immunity.Nature immunology · 2026Article
- Transient tertiary structure in intrinsically disordered proteins revealed by multithermal enhanced sampling.Nature communications · 2026Article
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Androgen Receptor Point Mutations: A Mechanism of Therapeutic Resistance and a Framework for Rational Drug Design.Cancers · 2026Review
- Dynamic yet well-defined organization of the FUS RGG3 dense phase.Communications chemistry · 2026Article
- Oligomerization enables the selective targeting of an intrinsically disordered region by a small molecule.Science advances · 2026Article
- Biomolecular Condensates Dictate the Folding Landscape of Proteins.bioRxiv : the preprint server for biology · 2026Article
- Decoding intrinsically disordered regions in biomolecular condensates.Fundamental research · 2026Review
- How small molecules stabilize oligomers of a phase-separating disordered protein.bioRxiv : the preprint server for biology · 2025Article
- Determining accurate conformational ensembles of intrinsically disordered proteins at atomic resolution.Nature communications · 2025Article
- Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation.bioRxiv : the preprint server for biology · 2025Article
- DIRseq: a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.bioRxiv : the preprint server for biology · 2025Article
- Biological insights from integrative modeling of intrinsically disordered protein systems.Current opinion in structural biology · 2025Review
- Phosphorylation-Regulated Conformational Diversity and Topological Dynamics of an Intrinsically Disordered Nuclear Receptor.The journal of physical chemistry. B · 2025Article
- Prediction of Small-Molecule Partitioning into Biomolecular Condensates from Simulation.JACS Au · 2025Article
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 at 2 institutions in 2 countries.
Funding
Abstract
Intrinsically disordered proteins, which do not adopt well-defined structures under physiological conditions, are implicated in many human diseases. Small molecules that target the disordered transactivation domain of the androgen receptor have entered human trials for the treatment of castration-resistant prostate cancer (CRPC), but no structural or mechanistic rationale exists to explain their inhibition mechanisms or relative potencies. Here, we utilize all-atom molecular dynamics computer simulations to elucidate atomically detailed binding mechanisms of the compounds EPI-002 and EPI-7170 to the androgen receptor. Our simulations reveal that both compounds bind at the interface of two transiently helical regions and induce the formation of partially folded collapsed helical states. We find that EPI-7170 binds androgen receptor more tightly than EPI-002 and we identify a network of intermolecular interactions that drives higher affinity binding. Our results suggest strategies for developing more potent androgen receptor inhibitors and general strategies for disordered protein drug design.
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.