ReviewNature reviews. Drug discovery2024
Protein isoform-centric therapeutics: expanding targets and increasing specificity.
Review in Nature reviews. Drug discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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
16 citing papers in PubMed.
- Functional divergence of Capicua isoforms explains differential tissue vulnerability in neurological disease.Genes & development · 2026Article
- Technologies to measure and modulate protein subcellular localization.Nature reviews. Molecular cell biology · 2026Review
- Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms.Nature communications · 2026Article
- Engineering molecularly imprinted polymers for receptor-specific cancer therapeutics.Nanoscale · 2026Review
- Isoform-specific m6A deposition and coordinated splicing shape mammalian transcriptome evolution.Nature communications · 2026Article
- Computational identification of rare pathogenic genomic variants in esophageal cancer markers: Transcript-level analysis, sequence-based insights, and structural-functional impacts of non-synonymous SNPs.Biochemistry and biophysics reports · 2026Article
- Isoform-specific single-cell perturb-seq reveals distinct functions of alternative promoters in drug response.Nucleic acids research · 2026Article
- IsoProDB: an integrated map of human protein isoforms for accelerated research.Database : the journal of biological databases and curation · 2026Article
- Neg-entropy is the true drug target for chronic diseases.Acta pharmaceutica Sinica. B · 2026Review
- Proteoformics-driven new concept of human growth hormone in clinical endocrinology.Frontiers in endocrinology · 2026Review
- Mapping the Role of Monomer Conformation in the Amyloid Formation of α-Synuclein Splice Variants.Journal of the American Chemical Society · 2025Article
- Functional divergence of Capicua isoforms explains differential tissue vulnerability in neurological disease.bioRxiv : the preprint server for biology · 2025Article
- Tau-Targeted Therapeutic Strategies: Mechanistic Targets, Clinical Pipelines, and Analysis of Failures.Cells · 2025Review
- A high-resolution data set of fatty acid-binding protein structures. II. Crystallographic overview, ligand classes and binding pose.Acta crystallographica. Section D, Structural biology · 2025Article
- More than microglia: myeloid cells and biomarkers in neurodegeneration.Frontiers in neuroscience · 2024Review
- Protein "purity," proteoforms, and the albuminome: critical observations on proteome and systems complexity.Frontiers in cell and developmental biology · 2024Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most protein-coding genes produce multiple protein isoforms; however, these isoforms are commonly neglected in drug discovery. The expression of protein isoforms can be specific to a disease, tissue and/or developmental stage, and this specific expression can be harnessed to achieve greater drug specificity than pan-targeting of all gene products and to enable improved treatments for diseases caused by aberrant protein isoform production. In recent years, several protein isoform-centric therapeutics have been developed. Here, we collate these studies and clinical trials to highlight three distinct but overlapping modes of action for protein isoform-centric drugs: isoform switching, isoform introduction or depletion, and modulation of isoform activity. In addition, we discuss how protein isoforms can be used clinically as targets for cell type-specific drug delivery and immunotherapy, diagnostic biomarkers and sources of cancer neoantigens. Collectively, we emphasize the value of a focus on isoforms as a route to discovering drugs with greater specificity and fewer adverse effects. This approach could enable the targeting of proteins for which pan-inhibition of all isoforms is toxic and poorly tolerated.
Indexed as
Identifiers
39232238What Socratic 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 Socratic graph.