ArticleFrontiers in chemistry2021
Development of Indole Alkaloid-Type Dual Immune Checkpoint Inhibitors Against CTLA-4 and PD-L1 Based on Diversity-Enhanced Extracts.
Article in Frontiers in chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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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
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles.Frontiers in pharmacology · 2022Pooled it
- New semisynthetic α-glucosidase inhibitor from a doubly-chemically engineered extract.Natural products and bioprospecting · 2025Article
- Chemically engineered essential oils prepared through thiocyanation under solvent-free conditions: chemical and bioactivity alteration.Natural products and bioprospecting · 2024Article
- Photoreaction products of extract from the fruiting bodies of Polyozellus multiplex.Journal of natural medicines · 2024Article
- Review
- Article
- Emerging Trends and Research Foci in Tumor Microenvironment of Pancreatic Cancer: A Bibliometric and Visualized Study.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer immunotherapy involves the use of the immune system for cancer treatment. Recently, immune checkpoint-blocking antibodies have become integral for the treatment of some cancers. However, small molecules exhibit advantages over monoclonal antibody drugs, such as cell penetration, long half-life, and low manufacturing costs, and the possibility of oral administration. Thus, it is imperative to develop small-molecule immune checkpoint inhibitors. Previously, we have screened a library of synthetic indole-alkaloid-type compounds, which are produced by diversity-enhanced extracts of Japanese cornelian cherry, and reported that an unnatural pentacyclic compound inhibits CTLA-4 gene expression. In this study, immune checkpoint inhibitors with increased potency were developed by introducing substituents and conversion of functional groups based on the unnatural pentacyclic compound. The developed compounds suppressed not only CTLA-4 and PD-L1 gene expression but also protein expression on the cell surface. Their efficacy was not as potent as that of the existing small-molecule immune checkpoint inhibitors, but, to the best of our knowledge, the developed compounds are the first reported dual small-molecule inhibitors of CTLA-4 and PD-L1.
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Registered trials
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