ArticleEuropean journal of immunology2021
Icaritin inhibits PD-L1 expression by Targeting Protein IκB Kinase α.
Article in European journal of immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 34 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.
Comparison of Efficacy and Safety of Icaritin Versus Cinobufotalin in First-line Treatment of Advanced Hepatocellular Carcinoma Subjects: a Multicenter, Randomized, Double-blind, Double-dummy Phase III Clinical Trial
Comparison of Efficacy and Safety of Icaritin Versus Sorafenib in First-line Treatment of PD-L1 Positive Advanced Hepatocellular Carcinoma Subjects: a Multicenter, Randomized, Opened Phase III Clinical Trial
Who cites it
34 citing papers in PubMed, 64 citations in OpenAlex.
- Icaritin Sensitizes Hepatocellular Carcinoma to PD-L1 Therapy by NQO1-Dependent Ferroptosis Induction.Phytotherapy research : PTR · 2026Article
- Quantitative Structure-Activity Relationship Approaches for Exploring the Anticancer Potential of Flavonoids.Chemistry & biodiversity · 2026Review
- A comprehensive narrative review ofJournal of pharmaceutical analysis · 2026Review
- Gut microbial metabolites targeting JUN in renal cell carcinoma via IL-17 signaling pathway: network pharmacology approach.Molecular diversity · 2026Article
- Dual role of icaritin in attenuating allograft rejection and exerting antitumor effects in mice.Frontiers in immunology · 2026Article
- Efficacy analysis of icaritin combined with transarterial chemoembolization in hepatocellular carcinoma stratified by different child-pugh classes.Frontiers in immunology · 2026Article
- Icariin mediates autophagy and apoptosis of hepatocellular carcinoma cells induced by the β-catenin signaling pathway through lncRNA LOXL1-AS1.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Natural anti-cancer products: insights from herbal medicine.Chinese medicine · 2025Review
- Advances in research on flavonoids in tumor immunotherapy (Review).Molecular medicine reports · 2025Review
- Flavonoids in the Treatment of Non-small Cell Lung Cancer via Immunomodulation: Progress to Date.Molecular diagnosis & therapy · 2025Review
- Dietary impacts on prostate cancer immunotherapy.Immunotherapy · 2025Review
- First-Line Treatment of Icaritin and Thalidomide in a Patient With Hepatocellular Carcinoma With PR: A Case Report.Cancer reports (Hoboken, N.J.) · 2025Article
- Identification and validation of icaritin-associated prognostic genes in hepatocellular carcinoma through network pharmacology, bioinformatics analysis, and cellular experiments.Frontiers in immunology · 2025Article
- A bibliometric and visualization analysis of the role of traditional Chinese medicine in cancer immunotherapy.Frontiers in immunology · 2025Article
- Traditional Chinese Medicine Monomers and Their Derivatives as a Promising Therapeutic Tool for Hepatocellular Carcinoma by Activation of Mitophagy.Drug design, development and therapy · 2025Review
- Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy.Military Medical Research · 2024Review
- Small-molecule-based targeted therapy in liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery.Molecular cancer · 2024Review
- Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus: A case report and review of literature.World journal of clinical cases · 2024Article
- MYC Oncogene: A Druggable Target for Treating Cancers with Natural Products.Aging and disease · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Icaritin, a small molecule currently being investigated in phase III clinical trials in China (NCT03236636 and NCT03236649) for treatment of advanced hepatocellular carcinoma (HCC), is a prenylflavonoid derivative obtained from the Epimedium genus. Previously, it was found that Icaritin decreased the expression of PD-L1, but its direct molecular targets and the underlying mechanisms have not been identified. In this study, we report the identification of IKK-α as the protein target of Icaritin by biotin-based affinity binding assay. The further mutagenesis assay has provided evidence that C46 and C178 in IKK-α were essential amino acids for Icaritin binding to IKK-α, revealing the binding sites of Icaritin to IKK-α for the first time. Functionally, Icaritin inhibited the NF-κB signalling pathway by blocking IKK complex formation, which led to decreased nuclear translocation of NF-κB p65, and subsequent downregulation of PD-L1 expression in a dose-dependent manner. More importantly, PD-L1-positive patients exhibited longer overall survival upon Icaritin therapy. Finally, Icaritin in combination with checkpoints antibodies, such as α-PD-1, has demonstrated much better efficacy than any single therapy in animal models. This is the first report that anticancer effects of Icaritin are mediated, at least in part, by impairing functions of IKK-α.
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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.