icaritin (SNG-162) / Shenogen Pharma - LARVOL DELTA

Identification and validation of icaritin-associated prognostic genes in hepatocellular carcinoma through network pharmacology, bioinformatics analysis, and cellular experiments. (PubMed, Front Immunol) - "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."

Biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CA9 • CYP2C9 • FABP5 • UCK2

Bioinspired honeycomb-mimetic adaptive hyaluronic acid hydrogel composite scaffold: intelligent prevention and treatment of infection of bone implants and promotion of bone repair. (PubMed, Mater Today Bio) - "The scaffold composed of an intermittently 3D low-temperature deposition printing honeycomb-shaped Poly(lactic-co-glycolic acid)/β-tricalcium phosphate icaritin (PTI) outer layer, maintaining the mechanical strength(elastic modulus ∼0.8 MPa) and osteogenic activity required for bone defect repair. Its core encapsulates hyaluronic acid (HA) hydrogel loaded with vancomycin(Van), serving as an intelligent "enzyme-responsive" unit...Simultaneously, the hydrogel inner layer exhibited outstanding biocompatibility, synergistically promoting the proliferation, migration, and in vitro osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs). In a rabbit tibial defect infection model, the scaffold successfully mimicked the beehive's active defense mechanism, effectively suppressing Methicillin-resistant Staphylococcus aureus (MRSA) infection within 14 days post-implantation, achieveing simultaneous and ideal bone repair outcomes."

Journal • Infectious Disease

Icaritin Ameliorates Cisplatin-Induced Mitochondrial Metabolic Dysfunction-Associated Nephrotoxicity and Synergistically Potentiates Its Antitumor Efficacy. (PubMed, Adv Sci (Weinh)) - "Combinatorial treatment with ICA not only ameliorates CDDP-induced nephrotoxicity but also enhances its anti-cancer efficacy. Taken together, these findings provide novel mechanistic insights into CDDP nephrotoxicity and propose a dual-function therapeutic strategy to optimize CDDP-based cancer therapy while minimizing renal damage."

Journal • Metabolic Disorders • Oncology • Renal Disease

Efficient multi-enzyme system for icaritin production from naringenin with synchronous prenol utilization in Escherichia coli. (PubMed, Int J Biol Macromol) - "With the combination of these strategies, 80.8 ± 3.6 mg/L ICT could be produced from NAR and prenol in the recombinant E. coli, from the original 0 % degree of conversion. The systematic engineering of multi-enzyme system for ICT biosynthesis has laid the foundation for the large-scale ICT production using the industrially important E. coli chassis cell."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Treatment of osteoporotic bone defects with carboxymethyl chitosan based biomimetic mineralized hydrogel loaded with icaritin. (PubMed, Int J Biol Macromol) - "Using carboxymethyl chitosan (CMCS) as the matrix, it cross-links alendronic acid (ALN) with the natural product genipin (GNP), aiming to promote bone regeneration in osteoporotic conditions. This compound is designated ICT@CMCS/ALN."

Journal • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

A Multimodal Energy-Depletion Strategy for Cooperative Tumor Metabolism Regulation in Enhanced Cancer Therapy. (PubMed, Biomater Res) - "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."

Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • CD8

Epimedii Folium flavonoids: A double-edged sword effect on the liver, a dual exploration of efficacy and toxicity. (PubMed, J Pharm Anal) - "Pharmacokinetic studies, especially on icaritin, indicate that it undergoes isopentenyl dehydrogenation, glycosylation, and glucuronidation in vivo, contributing to its pharmacological effects...We also summarize and discuss the pharmacokinetics of these flavonoids, highlighting how their metabolism affects therapeutic efficacy and toxicity. Lastly, we propose strategies to mitigate liver injury, providing new perspectives on the safe use of Epimedii Folium."

Journal • Review • Hepatology • Liver Failure

Novel senescence inducer ICA-11c, a derivative of icaritin, YAP-dependently suppresses hepatocellular carcinoma cells. (PubMed, Chem Biol Interact) - "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."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CDKN1A

A Prospective Study of Interventional Therapy Combined with Sintilimab, Bevacizumab, and Icaritin in Patients with Unresectable Hepatocellular Carcinoma (HCC). (ChiCTR) - P2 | N=60 | Recruiting | Sponsor: Sichuan Provincial People's Hospital; Sichuan Provincial People's Hospital

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

A prospective, single-arm clinical study of icaritin combination with gemcitabine and nab-pacitaxel as first-line therapy for advanced pancreatic ductal adenocarcinoma (ESMO 2025) - P=N/A | "Gemcitabine plus nab-paclitaxel (AG) is the standard treatment for advanced pancreatic ductal adenocarcinoma (PDAC). Legal entity responsible for the study Sir Run Run Shaw Hospital Zhejiang University School of Medicine. Funding Has not received any funding."

Clinical • Combination therapy • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

All-in-One 3D-Printed MXene/PLA/Icaritin (MXPI) Composite Scaffold Promotes Efficient Bone Repair for Intervertebral Fusion via NIR-Mediated Mild Photothermal Therapy (MPTT). (PubMed, ACS Appl Mater Interfaces) - "Compared to control scaffolds, MXPI exhibited superior fusion efficiency and bone regeneration within identical observation periods. Thus, this NIR-responsive MXPI scaffold provides a feasible and effective strategy for enhancing bone repair in spinal fusion applications."

Journal

Icaritin inhibits osteoclast differentiation and reduces bone loss by targeting ESR1 to inhibit miR503/RANK pathway. (PubMed, Front Pharmacol) - "Antagomir-503-5p significantly reduced the regulatory effect of ICT on OC differentiation, as well as the expression of genes related to OC differentiation. Taken together, our study confirmed that ESR1 is the direct target of ICT, and Asparagine at 455 is the direct binding site of ICT, and ICT inhibits OC differentiation and reduces bone loss by targeting ESR1 to upregulate miR503 level and weaken miR503/RANK pathway."

Journal • Metabolic Disorders • Osteoporosis • Rheumatology • ER • MIR503 • MMP9 • NFATC1 • TNFRSF11B • TRAP

Targeting FDX1 with Icaritin Attenuates Neuronal Cuproptosis by Reconciling Mitochondrial Fission-Fusion Dynamics and Bioenergetic Homeostasis. (PubMed, Free Radic Biol Med) - "Thus, this study was aimed to investigate ICT's protective mechanisms against cuproptosis induced by the cupric sulfate and copper ionophore elesclomol (Cu-ES) in HT22 hippocampal neuronal cells. Furthermore, ICT rescued mitochondrial dynamics by promoting fusion and inhibiting fission. Our findings demonstrate ICT is a potent inhibitor of neuronal cuproptosis, targeting FDX1 to alleviate mitochondrial oxidative stress, dysfunction, and dynamics disorder, presenting a promising therapeutic strategy."

Journal • Metabolic Disorders • ATP7B • DLAT • FDX1 • SLC31A1

Single-arm Clinical Trial of TACE in Combination With Icaritin as Adjuvant Therapy After Surgery in Patients With Hepatocellular Carcinoma at High Risk of Recurrence (clinicaltrials.gov) - P2/3 | N=30 | Recruiting | Sponsor: Zhujiang Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatocellular Cancer • Oncology • Solid Tumor

Elucidating the Pharmacological Basis of Xianling Cifang Granules Against Breast Cancer. A Metabolomic Profiling Study. (PubMed, Drug Des Devel Ther) - "Icaritin (a metabolite derived from Epimedium brevicornu Maxim) was identified as a pivotal constituent due to its high bioavailability and established anti-BC activity, specifically inducing redox-mediated apoptosis via the SIRT6/NF-κB pathway and modulating the immunosuppressive microenvironment in triple-negative breast cancer (TNBC)...These findings provide robust pharmacological evidence supporting the clinical application of XLCF against BC and demonstrate the value of combining metabolomics with target prediction for Traditional Chinese Medicine (TCM) research. Experimental validation of the identified targets is warranted."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKR1B1 • SIRT6

hUC-MSCs and derived exosomes attenuate DEX-induced muscle atrophy through modulation of estrogen signaling pathway. (PubMed, Stem Cell Res Ther) - "This study underscores the potential of hUC-MSCs and their derived exosomes as a novel, safe, and effective therapeutic strategies for sarcopenia, offering promising avenues for clinical application."

IO biomarker • Journal • Inflammation • Muscular Atrophy • Sarcopenia • BAX • BCL2 • BECN1 • CASP3 • FOXO3 • IL1B • IL6 • TNFA

Icaritin protects against airway inflammation by inhibiting the TLR4/NF-κB pathway in vivo and in vitro. (PubMed, Pulm Pharmacol Ther) - "Further mechanistic studies showed that Icaritin reduces TLR4-induced inflammatory factor expression and blocks TLR4-activated NF-κB pathway in BEAS-2B cells. These findings demonstrate for the first time that Icaritin suppresses airway inflammation in asthma by inhibiting the TLR4/NF-κB pathway, suggesting its potential as a therapeutic agent for asthma."

Journal • Preclinical • Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • NFKBIA

ICT-HCC: Individualized Comprehensive Treatment for Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Nanjing Tianyinshan Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Hepatocellular Cancer • Oncology • Solid Tumor

Icariin and related metabolites in fibrosis management: pharmacological properties and molecular mechanism. (PubMed, Front Pharmacol) - "Recent advances in extraction methods and drug delivery systems have improved the pharmacokinetic properties of ICA and related active metabolites, including icaritin and icariside II. These metabolites exert antifibrotic effects through multifaceted mechanisms, including anti-inflammatory and antioxidant activities, mitochondrial function modulation, apoptosis regulation, and autophagy. This review summarizes current insights into the molecular pathways through which ICA and related metabolites attenuate fibrosis, thereby supporting their potential for clinical translation in antifibrotic therapy."

Journal • Review • Fibrosis • Immunology

A multicenter, single-arm intervention study of Icaritin combined with mFOLFOX chemotherapy in the second-line treatment of malignant biliary tract tumors (ChiCTR) - P4 | N=31 | Not yet recruiting | Sponsor: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

New P4 trial • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CA 19-9

Pharmacokinetic Study of Icaritin Soft Capsules in Healthy Chinese Subjects (ChiCTR) - P1 | N=10 | Not yet recruiting | Sponsor: Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine; Shuguang Hospital Affiliated to Shanghai University of Traditiona

New P1 trial • Hepatocellular Cancer • Oncology • Solid Tumor

A real-world study of the initial use of acoradine in patients with hepatocellular carcinoma after liver transplantation (ChiCTR) - P=N/A | N=100 | Recruiting | Sponsor: The Affiliated Hospital of Qingdao University; The Affiliated Hospital of Qingdao University

New trial • Real-world evidence • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation

Icaritin and lenvatinib treatment for unresectable localized progressive pancreatic cancer: a report of six cases. (PubMed, Ann Med) - "These results highlight the potential efficacy of this multifaceted approach. Integrating icaritin with chemotherapy, immunotherapy, and/or targeted therapies shows potential as an exploratory approach in managing advanced, locally progressive, or metastatic pancreatic cancer, though further validation is required."

Journal • Oncology • Pancreatic Cancer • Solid Tumor

A prospective, single-arm clinical study of icaritin in combination with gemcitabine and nab-pacitaxel in patients with advanced pancreatic ductal adenocarcinoma not received prior systemic therapy. (ASCO 2025) - P=N/A | "Although trials with larger sample size are needed for further validation, this experimental phase II study indicates Icaritin as a promising role in combination with chemotherapy for the treatment of advanced PDAC. Clinical trial information: ChiCTR2300077907."

Clinical • Combination therapy • Metastases • Anemia • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia

Icaritin induces paraptosis in hepatocellular carcinoma cells by targeting BHLHE40 via endoplasmic reticulum stress and mitochondrial dysfunction. (PubMed, Phytomedicine) - "These results highlight the potent anticancer effects of icaritin, particularly its ability to induce paraptosis by targeting BHLHE40. This study provides a comprehensive understanding of the anticancer mechanisms of icaritin and suggests that targeting BHLHE40 represents a novel therapeutic strategy for enhancing the efficacy of cancer treatment."

Journal • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • ATF4 • DDIT3 • LMNA • PARP1 • TCF4