ArticleNature communications2015
Target engagement and drug residence time can be observed in living cells with BRET.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 281 citations in OpenAlex.
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- Quantification of Binding of Small Molecules to Native Kinases by Flow Cytometry Reveals Divergence from Biochemical Affinities.Journal of the American Chemical Society · 2026Article
- Peptides as programmable molecular scaffolds: from chemical synthesis and engineering to translational medicine.RSC chemical biology · 2026Review
- Global protein-ligand binding affinity profiling via photocatalytic labeling.Nature communications · 2026Article
- Advances in BRET probes for intracellular target engagement studies.Nature chemical biology · 2026Review
- Cellular Target Engagement and Dissociation Kinetics of Class I-Selective Histone Deacetylase (HDAC) Inhibitors.International journal of molecular sciences · 2026Article
- Cellular Context Influences Kinase Inhibitor Selectivity.Journal of medicinal chemistry · 2026Article
- Development of cell-active BRD4-D1 selective inhibitors to decode the role of BET proteins in LPS-mediated liver inflammation.European journal of medicinal chemistry · 2026Article
- Small-molecule probes based on natural products: Elucidation of drug-target mechanisms in stroke.Journal of pharmaceutical analysis · 2025Review
- Thermal shift engagement assay for Class IIA histone deacetylase inhibitor screening.Results in chemistry · 2025Article
- Discovery and Characterization of Cell-Permeable Inhibitors ofACS infectious diseases · 2025Article
- Cellular Selectivity Analyses Reveal Distinguishing Profiles for Type II Kinase Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma.Cancer research communications · 2025Article
- One Tracer, Dual Platforms: Unlocking Versatility of Fluorescent Probes in TR-FRET and NanoBRET Target Engagement Assays.ACS medicinal chemistry letters · 2025Article
- Live-Cell NanoBRET Assay to Measure AKT Inhibitor Binding to Conformational States of AKT.ACS chemical biology · 2025Article
- A Molecular Glue Approach to Control the Half-Life of CRISPR-Based Technologies.Journal of the American Chemical Society · 2025Article
- Target Engagement Assays in Early Drug Discovery.Journal of medicinal chemistry · 2025Review
- Efficacy and Toxicity Analysis of Selective BET Bromodomain Inhibitors in Models of Inflammatory Liver Disease.Journal of medicinal chemistry · 2025Article
66 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
The therapeutic action of drugs is predicated on their physical engagement with cellular targets. Here we describe a broadly applicable method using bioluminescence resonance energy transfer (BRET) to reveal the binding characteristics of a drug with selected targets within intact cells. Cell-permeable fluorescent tracers are used in a competitive binding format to quantify drug engagement with the target proteins fused to Nanoluc luciferase. The approach enabled us to profile isozyme-specific engagement and binding kinetics for a panel of histone deacetylase (HDAC) inhibitors. Our analysis was directed particularly to the clinically approved prodrug FK228 (Istodax/Romidepsin) because of its unique and largely unexplained mechanism of sustained intracellular action. Analysis of the binding kinetics by BRET revealed remarkably long intracellular residence times for FK228 at HDAC1, explaining the protracted intracellular behaviour of this prodrug. Our results demonstrate a novel application of BRET for assessing target engagement within the complex milieu of the intracellular environment.
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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.