icaritin (SNG-162)

This study establishes TKFC as an endogenous ferroptosis regulator and direct molecular target of Icaritin in HCC, positioning it as both a prognostic biomarker and therapeutic target for precision therapy.

In the tumor-bearing murine heart transplantation model, ICT potentiated the immunosuppressive efficacy of tacrolimus while reducing the tumor burden. While exerting antitumor effects, ICT attenuates allograft rejection by targeting the CEBPB/PIM1 axis, thereby suppressing CD4+ T-cell activation, proliferation, and Th1 differentiation.

Our findings demonstrate that icaritin triggered NQO1-mediated ferroptosis and remodeled TME to enhance NK cell recruitment and PD-L1 therapy efficacy. This provides rationale for evaluating icaritin-based combination immunotherapy in HCC through dual action on ferroptosis and NK cell activation.

Molecular docking simulations demonstrated that the interation energy between CES2 and icaritin was significantly higher than that with cisplatin (a reported CES2 activator), which might suggest that CES2 has a higher affinity for icaritin than cisplatin. These findings have important clinical significance for reducing chemotherapy drug resistance in cancer patients. Abbreviations: CES2, Carboxylesterase 2; CRC, Colorectal cancer; CPT-11, Irinotecan; CYP3A, Cytochrome P450 3A; NR, Nuclear receptor; P53, Tumor protein p53; PPAR-α, Peroxisome proliferator-activated receptor α; PXR, Pregnane X receptor; SN-38, 7-Ethyl-10-hydroxycamptothecin; UGT1A1, UDP-glucuronosyltransferase 1A1.

P=N/A, N=24, Completed, Jiangsu Provincial People's HospitalnNanjing Tianyinshan Hospital; Jiangsu Provincial People's Hospital

Combining TSA&ICT-MP with α-PD-1 achieved a 70.33% suppression rate of lung metastasis and prolonged survival in murine models. This approach offers a promising strategy to enhance the efficacy of melanoma immunotherapy.

P2, N=30, Recruiting, Northern Jiangsu People's Hospital

Considering the metabolism of icariin into icaritin in vivo, icaritin was selected for in vitro study. Furthermore, MK2206 upregulated the expression levels of cleaved caspase-3 and p-p53(Ser15), as well as the Bax/Bcl-2 ratio, and downregulated the expression levels of p-Akt(Ser473) and p-MDM2(Ser166). These findings suggest that icariin protects against high-fat diet-induced spermatogonium apoptosis potentially through regulation of Akt/MDM2/p53 signaling and promotion of mitochondrial fusion.

In vitro validation confirmed that ICT suppresses HepG2 and Huh7 cells proliferation and migration in a dose-dependent manner, while molecular analyses demonstrated that ICT treatment significantly downregulates CA9, UCK2, and FABP5 expression and simultaneously upregulates CYP2C9, thereby supporting its role in modulating critical oncogenic pathways. Modulation of ICT-targeted genes was found to effectively suppress HCC progression, underscoring their potential value as prognostic biomarkers and ideal therapeutic targets for the treatment of HCC.

Herein, this work introduces an Artesunate/Icaritin (ART/ICA) hybrid nanoplatform derived from herbal medicine that employs a multimodal energy depletion strategy for malignant tumor therapy...In vivo evaluations using various tumor models, including hepatocellular carcinoma transgenic mouse models, confirmed significantly enhanced antitumor efficacy, while subcutaneous tumor models showed a tumor inhibition rate exceeding 97%, far surpassing the effects of ART or ICA alone. Furthermore, flow cytometry analyses also confirmed that this strategy modulated the tumor microenvironment by enhancing the infiltration of cytotoxic CD8+ T cells and promoting dendritic cell maturation, while the incorporation of a CD47-targeting nanobody further strengthened immune activation and contributed to improved antitumor efficacy.

Our findings not only show that ICA-11c served as a potential YAP regulator for the treatment of hepatocellular carcinoma, but also explore the relationship between YAP and cellular senescence. This study suggests that ICA-11c may be a potential novel inducer of cellular senescence in hepatocellular carcinoma cells.

P2, N=60, Recruiting, Sichuan Provincial People's Hospital; Sichuan Provincial People's Hospital