ArticleJournal of molecular cell biology2024
A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex.
Article in Journal of molecular cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 12 citations in OpenAlex.
- Neo-Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein.Angewandte Chemie (International ed. in English) · 2026Article
- Stalling the Enemy: Targeting Nsp13 for Next-Generation SARS-CoV-2 Antivirals.International journal of molecular sciences · 2026Article
- Article
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- Optimization and development of a high-throughput TR-FRET screening assay for SLIT2/ROBO1 interaction.SLAS discovery : advancing life sciences R & D · 2025Article
- Multiplexed Dark FRET Biosensors: An accessible live-cell platform for target- and cell-specific monitoring of protein-protein interactions in 2D and 3D model systems.Research square · 2025Article
- Evaluation of molecular glue-induced neomorphic protein-protein interaction with a cell lysate-based time-resolved fluorescence resonance energy transfer assay.ASPET discovery · 2025Article
- UnravelingCancer drug resistance (Alhambra, Calif.) · 2025Article
- Application of Fluorescence- and Bioluminescence-Based Biosensors in Cancer Drug Discovery.Biosensors · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The transforming growth factor-beta (TGFβ) signaling pathway plays crucial roles in the establishment of an immunosuppressive tumor microenvironment, making anti-TGFβ agents a significant area of interest in cancer immunotherapy. However, the clinical translation of current anti-TGFβ agents that target upstream cytokines and receptors remains challenging. Therefore, the development of small-molecule inhibitors specifically targeting SMAD4, the downstream master regulator of the TGFβ pathway, would offer an alternative approach with significant therapeutic potential for anti-TGFβ signaling. In this study, we present the development of a cell lysate-based multiplexed time-resolved fluorescence resonance energy transfer (TR-FRET) assay in an ultrahigh-throughput screening (uHTS) 1536-well plate format. This assay enables simultaneous monitoring of the protein‒protein interaction between SMAD4 and SMAD3, as well as the protein‒DNA interaction between SMADs and their consensus DNA-binding motif. The multiplexed TR-FRET assay exhibits high sensitivity, allowing the dynamic analysis of the SMAD4-SMAD3-DNA complex at single-amino acid resolution. Moreover, the multiplexed uHTS assay demonstrates robustness for screening small-molecule inhibitors. Through a pilot screening of an FDA-approved bioactive compound library, we identified gambogic acid and gambogenic acid as potential hit compounds. These proof-of-concept findings underscore the utility of our optimized multiplexed TR-FRET platform for large-scale screening to discover small-molecule inhibitors that target the SMAD4-SMAD3-DNA complex as novel anti-TGFβ signaling agents.
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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.