Icaritin inhibits PD‐L1 expression by Targeting Protein IκB Kinase α

  title={Icaritin inhibits PD‐L1 expression by Targeting Protein I$\kappa$B Kinase $\alpha$},
  author={Dongliang Mo and Hai Zhu and Jun Wang and Haibang Hao and Yu-ming Guo and Jiaojiao Wang and Xuelian Han and Liangfeng Zou and Zhongwan Li and Hua Yao and Jinsong Zhu and Junma Zhou and Yong Peng and Jian Li and Kun Meng},
  journal={European Journal of Immunology},
  pages={978 - 988}
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… 
Icaritin ameliorates extracellular microparticles-induced inflammatory pre-metastatic niche via modulating the cGAS-STING signaling.
It was demonstrated that ICT could inhibit the pulmonary metastasis of B16BL6 melanoma cells in mice via interfering with PMN and a new binding mechanism between STING and ICT for the inhibition of transduction of the STING signaling pathway was highlighted.
A Mini-Review of Flavone Isomers Apigenin and Genistein in Prostate Cancer Treatment
A look into the progress of apigenin and genistein, which are isomers, in treating PCa in the past decade and how these two isomers can both target the same signaling pathways; they also are found to work differently in PCa cells.
Phytochemicals in Cancer Immune Checkpoint Inhibitor Therapy
Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules, and summarizes druggable immune checkpoints and their regulatory factors.
Chinese Herbal Medicine for Primary Liver Cancer Therapy: Perspectives and Challenges
A deeper the understanding of CHMs as PLC treatments is provided and ideas for the development of new natural drugs against PLC are provided.
Advances in drug development for hepatocellular carcinoma: clinical trials and potential therapeutic targets
FDA-approved agents for HCC are summarized, promising agents evaluated in clinical phase I/II/III trials are elucidated, and emerging targets for H CC treatment are identified.


Icaritin, a novel FASN inhibitor, exerts anti-melanoma activities through IGF-1R/STAT3 signaling
It was reported that IT exerted anti-melanoma activities, and these effects were partially due to inhibition of FASN/IGF-1R/STAT3 signaling.
Icaritin induces apoptosis of HepG2 cells via the JNK1 signaling pathway independent of the estrogen receptor.
A novel pro-apoptotic activity of icaritin mediated via the JNK1 signaling pathway that is not associated with ER in HepG2 cells is suggested.
Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways
It is demonstrated that icaritin inhibits the proliferation of human AML cell lines NB4, HL60, and U937, in a dose- and time-dependent manner and showed anti-leukemia activity on bone marrow mononuclear cells from 15 newly diagnosed AML patients, suggesting that icoritin is a promising candidate drug for the treatment of AML.
Identification of sphingosine kinase 1 (SphK1) as a primary target of icaritin in hepatocellular carcinoma cells
In summary, icaritin exerts potent anti-HCC activity in vitro and in vivo, and SphK1 inhibition could be the primary mechanism of its actions in HCC cells.
Icaritin Causes Sustained ERK1/2 Activation and Induces Apoptosis in Human Endometrial Cancer Cells
It is demonstrated that icaritin induced sustained ERK 1/2 activation and inhibited growth of endometrial cancer Hec1A cells, and provided a rational for preclinical and clinical evaluation of icar itin for endometricrial cancer therapy.
Icaritin promotes tumor T‐cell infiltration and induces antitumor immunity in mice
It is shown that icaritin can effectively decrease tumor burden of murine B16F10 melanoma and MC38 colorectal tumors in a T‐cell dependent manner and the combination of anti‐PD‐1/CTLA‐4 and icar itin significantly enhances antitumor ability and increases the efficacy of either treatment alone.
Mutation of cysteine 46 in IKK-beta increases inflammatory responses
It is suggested that Cys-46 is a novel drug-binding site for the inhibition of IKK-β, which contributes to cancer pathogenesis and inflammatory disease and is a potential therapeutic target.
The Flavonoid Apigenin Downregulates CDK1 by Directly Targeting Ribosomal Protein S9
Results suggest that apigenin induces G2/M arrest at least partially by directly binding and inhibiting RPS9 which enhances CDK1 expression.
Icaritin induces apoptotic and autophagic cell death in human glioblastoma cells.
Based on the findings, icaritin can be considered as a promising candidate therapeutic agent for treatment of GBM, though further studies are needed.