ArticleJournal of medicinal chemistry2025
Discovery of CD28-Targeted Small Molecule Inhibitors of T Cell Co-Stimulation Using Affinity Selection-Mass Spectrometry (AS-MS) and Ex Vivo Validation.
Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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
7 citing papers in PubMed.
- HTS-Oracle X: AI-Guided Prospective Discovery of Small Molecule Immune Checkpoint Binders.ACS medicinal chemistry letters · 2026Article
- AI-Enforced Ultra-Large Virtual Screening Discovers Potent CD28 Binders.Journal of chemical information and modeling · 2026Article
- An integrated biophysical fragment screening approach identifies novel binders of the CD28 immune receptor.Biochemistry and biophysics reports · 2026Article
- PANoptosis as a drug discovery framework: integrating cell death architecture with clinical translation.Genes and immunity · 2026Review
- Overcoming the undruggable barrier: Structure-guided discovery of a potent small molecule CD28 antagonist with translational potential.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Structure-based virtual screening identifies potent CD28 inhibitors that suppress T cell co-stimulation in cellular and mucosal models.European journal of medicinal chemistry · 2025Article
- Redefining the Diagnostic and Therapeutic Landscape of Non-Small Cell Lung Cancer in the Era of Precision Medicine.Journal of clinical medicine · 2025Review
Corrections and comments
- Update of
Authors and funding
4 authors.
Funding
Abstract
CD28 is a key T cell costimulatory receptor implicated in antitumor immunity and immune-related disorders, yet no small molecule modulators of CD28 have reached clinical development. Here, we report the discovery and characterization of small molecule CD28 antagonists identified through affinity selection-mass spectrometry (AS-MS). Subsequent catalog-based structure-activity relationship (SAR) optimization led to the identification of validated hits, 5MS-5 and 19MS-5, which exhibit direct CD28 binding and potent inhibition of CD28-B7 interactions in cellular reporter assays. Pharmacokinetic profiling demonstrated favorable solubility, metabolic stability, permeability, and oral exposure in vivo. Functionally, both compounds suppressed cytokine production in primary human T cells cocultured with tumor spheroids and human epithelial tissues, validating their ability to inhibit CD28-driven immune activation in physiologically relevant models. These findings establish 5MS-5 and 19MS-5 as promising CD28 inhibitors and provide a foundation for developing orally bioavailable immunomodulators targeting T cell costimulation.
Indexed as
Identifiers
What 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.