ArticleBJC reports2024
Artificial intelligence-powered discovery of small molecules inhibiting CTLA-4 in cancer.
Article in BJC reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Strategies for Identifying Molecules of Interest in Large Chemical Spaces.Journal of chemical information and modeling · 2026Article
- Immune Checkpoint-Based Therapies in Colorectal Cancer-Current Approaches and Future Perspectives.International journal of molecular sciences · 2026Review
- Precision oncology in the age of AI: lessons from AI-driven drug discovery and clinical translation.BJC reports · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Research on the Mechanism of "Cold Tumor" Formation and Immunotherapy for Its Transformation into "Hot Tumor".Oncology research · 2026Review
- Overcoming the undruggable barrier: Structure-guided discovery of a potent small molecule CD28 antagonist with translational potential.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Applications of artificial intelligence in non-small cell lung cancer: from precision diagnosis to personalized prognosis and therapy.Journal of translational medicine · 2025Review
- Review
- Discovery of CD28-Targeted Small Molecule Inhibitors of T Cell Co-Stimulation Using Affinity Selection-Mass Spectrometry (AS-MS) and Ex Vivo Validation.Journal of medicinal chemistry · 2025Article
- Study on the Molecular Dynamics of 2‑(4-Fluorophenyl)-6-methyl-4-(3- (trifluoromethyl)phenyl)-1,2-dihydrodipyrazolo[3,4-b:3',4'‑ACS omega · 2025Article
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- Integrating artificial intelligence into small molecule development for precision cancer immunomodulation therapy.npj drug discovery · 2025Review
- Digital Alchemy: The Rise of Machine and Deep Learning in Small-Molecule Drug Discovery.International journal of molecular sciences · 2025Review
- Negative Immune Checkpoint Inhibitors.Pharmaceutics · 2025Review
- Integrating AI into Cancer Immunotherapy-A Narrative Review of Current Applications and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- Malaria: Factors affecting disease severity, immune evasion mechanisms, and reversal of immune inhibition to enhance vaccine efficacy.PLoS pathogens · 2025Review
- Artificial Intelligence in Head and Neck Cancer: Innovations, Applications, and Future Directions.Current oncology (Toronto, Ont.) · 2024Review
- Future AI Will Most Likely Predict Antibody-Drug Conjugate Response in Oncology: A Review and Expert Opinion.Cancers · 2024Review
- A Comprehensive Computational Insight into the PD-L1 Binding to PD-1 and Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesCheckpoint inhibitors, which generate durable responses in many cancer patients, have revolutionized cancer immunotherapy. However, their therapeutic efficacy is limited, and immune-related adverse events are severe, especially for monoclonal antibody treatment directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which plays a pivotal role in preventing autoimmunity and fostering anticancer immunity by interacting with the B7 proteins CD80 and CD86. Small molecules impairing the CTLA-4/CD80 interaction have been developed; however, they directly target CD80, not CTLA-4. SUBJECTS/
methodsIn this study, we performed artificial intelligence (AI)-powered virtual screening of approximately ten million compounds to identify those targeting CTLA-4. We validated the hits molecules with biochemical, biophysical, immunological, and experimental animal assays.
resultsThe primary hits obtained from the virtual screening were successfully validated in vitro and in vivo. We then optimized lead compounds and obtained inhibitors (inhibitory concentration, 1 micromole) that disrupted the CTLA-4/CD80 interaction without degrading CTLA-4.
conclusionsSeveral compounds inhibited tumor development prophylactically and therapeutically in syngeneic and CTLA-4-humanized mice. Our findings support using AI-based frameworks to design small molecules targeting immune checkpoints for cancer therapy.
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.