ArticleASPET discovery2025
Evaluation of molecular glue-induced neomorphic protein-protein interaction with a cell lysate-based time-resolved fluorescence resonance energy transfer assay.
Article in ASPET discovery, 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.
- Epitope-guided Detection of a Molecular Glue-induced Ternary Complex Using Engineered Synthetic Antibody Fragments.Journal of molecular biology · 2026Article
- Neo-Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein.Angewandte Chemie (International ed. in English) · 2026Article
- Optimization and development of a high-throughput TR-FRET screening assay for SLIT2/ROBO1 interaction.SLAS discovery : advancing life sciences R & D · 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.
Funding
Abstract
Neo-protein-protein interactions (neoPPI) induced by mutated amino acid residues present a promising class of therapeutic targets for proximity pharmacology-enabled drug discovery. Small molecule compounds, such as cyclosporin and FK506, have the capability to mimic the mutational effect to create new interaction interfaces to enhance the interaction of a protein with an unrelated, or low affinity protein. Such small molecules can function as molecular glues to purposefully generate neoPPIs for physiological reprogramming and therapeutic intervention. Thus, an unbiased approach for the systematic discovery of neoPPI-inducing compounds is much needed to accelerate the proximity pharmacology field. With the demonstrated small molecule induced neoPPI of oncogenic KRAS with cyclophilin A (CYPA), here we report the development of a robust cell lysate-based time-resolved fluorescence resonance energy transfer (TR-FRET) assay to characterize KRAS-CYPA neoPPI inducing molecular glues. We show that the developed TR-FRET assay can monitor the induced interaction of CYPA with oncogenic KRAS variants, KRAS-G12C, G12D and G12V. The assay was optimized to achieve a robust performance in a miniaturized format, which was utilized to demonstrate the potent effect of RMC-7977, a known molecular glue, in inducing the KRAS-CYPA interaction. This validated assay platform allows for the characterization of molecular glue-induced KRAS-CYPA neoPPI, which is readily applicable to explore the vast chemical space for the discovery of novel KRAS-CYPA neoPPI inducers and can be generally applicable for unbiased discovery of proximity-inducing molecular glues.
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.