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

Icaritin and its N-Boc-amino acid ester derivatives: Chemistry, structure-activity relationships, and preliminary mechanistic insights. (PubMed, Eur J Med Chem) - "The N-Boc-l-proline ester M1 was the most potent α-glucosidase inhibitor (IC50 = 5.5 ± 0.5 nM), 1.5-fold and 2.0-fold more active than its parent ICT (8.3 ± 0.5 nM) and acarbose (11.0 ± 0.6 nM), and remained intact in simulated gastric and intestinal fluids...In palmitate-induced insulin-resistant HepG2 cells, M1 (20 μM) increased glucose consumption by 58.1% over the model group, lowered intracellular ROS to approximately 2.6-fold of control, and reduced lipid accumulation to a level comparable to metformin. These effects were accompanied by downregulation of glucose-6-phosphatase and upregulation of catalase, without significantly altering basal glucose consumption in normal HepG2 cells. Together, these findings establish a scalable route to ICT and demonstrate that esterification of its phenolic hydroxyl groups can modify α-glucosidase inhibition and cellular metabolic phenotypes, identifying M1 as a lead compound meriting in vivo validation."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CAT

Microglia-targeted Panax notoginseng polysaccharide nanoparticles alleviate Alzheimer's disease via AMPK-mTOR/HIF-1α-mediated immunometabolic reprogramming. (PubMed, Mater Today Bio) - "Through rational engineering via phenylboronic ester grafting, the polysaccharide backbone enables amphiphilic self-assembly and efficient co-loading of icaritin and tanshinone IIA, while allowing pathological reactive oxygen species (ROS)-triggered disassembly...Mechanistically, KPBIT@NPs activate AMP-activated protein kinase and suppress the mechanistic target of rapamycin/hypoxia-inducible factor 1α signaling axis, thereby reversing pathological glycolytic skewing and restoring mitochondrial oxidative metabolism...In AD animal models, KPBIT@NPs effectively restore cerebral energy metabolism, markedly reduce amyloid-β deposition, alleviate neuroinflammation, preserve neuronal integrity, and ultimately rescue cognitive deficits. This study establishes an innovative nanotherapeutic paradigm based on bioactive polysaccharides and offers a promising materials strategy for neurodegenerative diseases driven by coupled metabolic and inflammatory dysregulation."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Metabolic Disorders • AMPK • HIF1A • mTOR

Icaritin improves pregnancy outcomes in endometriosis by inhibiting ovarian granulosa cell senescence. (PubMed, Mol Biol Rep) - "These findings identify Ica as a GC senescence-inhibiting agent with therapeutic potential in EMS-associated infertility."

Journal • Endometriosis • Gynecology • Infertility • Musculoskeletal Pain • Oncology • Pain • Sexual Disorders • Women's Health

Efficacy analysis of icaritin combined with transarterial chemoembolization in hepatocellular carcinoma stratified by different child-pugh classes. (PubMed, Front Immunol) - "TACE combined with Icaritin was associated with improved survival outcomes, with the most consistent benefit observed in patients with Child-Pugh grade A liver function. In Child-Pugh grade B patients, the findings should be interpreted cautiously because of the limited subgroup size and insufficient statistical power."

Journal • Retrospective data • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Trifluoro-icaritin attenuates neuropathic pain-associated anxiety-like behaviors and hippocampal oxidative stress in rats. (PubMed, Neuroscience) - "These findings support context-dependent involvement of Sigma-1R-associated redox regulation in the effects of ICTF. They do not establish direct ICTF-Sigma-1R binding, pharmacological selectivity, or an anxiolytic effect independent of analgesia."

Journal • Preclinical • Immunology • Neuralgia • Pain • Psychiatry

Functional characterization of a novel flavonoid glycosyltransferase UGT89AD6 from Anemarrhena asphodeloides Bunge and mechanistic insights into its enzymatic O-glycosylation. (PubMed, Planta) - "In A. asphodeloides, icariside I is derived from the O-glycosylation of icaritin...Beyond this, the regioselectivity of UGT89AD6 might be shaped by hydrophobic interactions and hydrogen-bonding network, as well as shallow cavity of the binding pocket. This study contributes to the diversity of glycosyltransferases from monocotyledonous plants and provides a potential biocatalyst to synthesize high-value bioactive flavonoid glycosides."

Journal

An Overview of the Phytochemistry, Biological Activities and Therapeutic Potential of Epimedium spp. (PubMed, Plants (Basel)) - "are defined by their significant content of prenylated flavonol glycosides, including icariin, icaritin, icariside, baohuoside and epimedin A-C...Taken together, the data summarized here position Epimedium spp. as a valuable source of bioactive prenylated flavonoids, while underscoring that standardized methodologies and rigorous clinical trials are essential to translate this potential into validated therapeutic applications."

Journal • Review • Erectile Dysfunction • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology

Icaritin inhibits breast cancer through activating MT1X to promote ferroptosis and synergizing with NF-κB pathway suppression. (PubMed, Front Oncol) - "This study elucidates that ICT exerts anti-breast cancer effects by activating MT1X to induce ferroptosis and cooperatively inhibit the NF-κB signaling pathway. Our findings reveal a novel molecular mechanism of ICT against breast cancer, and provide a new therapeutic target and experimental basis for breast cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • GPX4 • MT1X • NFKBIA • SLC7A11

Efficacy and Safety of HAIC Plus Regorafenib and Icaritin in Advanced Hepatocellular Carcinoma After First-Line Lenvatinib Failure: A Retrospective Analysis. (PubMed, Anticancer Agents Med Chem) - "HAIC combined with regorafenib and icaritin shows enhanced efficacy and manageable toxicity in lenvatinib-refractory advanced HCC, with improved physical tolerance evidenced by reduced fatigue. The observed benefits of this triplet regimen warrant further prospective validation as a potential personalized secondline approach for Barcelona Clinic Liver Cancer stage C (BCLC-C) patients, pending confirmation in randomized controlled trials."

Journal • Retrospective data • Fatigue • Hepatocellular Cancer • Immunology • Liver Cancer • Oncology • Pain • Solid Tumor

Longitudinal drug response assessment of tumor organoids based on optical attenuation coefficient and multi-dimensional morphological characterization. (PubMed, Biomed Opt Express) - "Using intrahepatic cholangiocarcinoma (iCCA) PDTOs treated with icaritin, we found that OAC exhibited a significant dose-dependent increase (up to 32.8% at 80 μM compared to control), accompanied by a morphological transition of cystic organoids into solid phenotypes. Furthermore, independent experiments with first-line chemotherapeutics (e.g., 5-Fluorouracil, Gemcitabine) and combinatorial regimens indicated the model's potential generalizability (r = 0.887). This method overcomes the limitations of destructive, single-metric evaluations, providing a quantitative and non-destructive platform for high-throughput drug screening and personalized treatment decision-making."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

Trifluoro-icaritin mitigates spared nerve injury-induced neuropathic pain by upregulating spinal α7nAChR through suppressing ferroptosis. (PubMed, J Ethnopharmacol) - "We found that spinal ferroptosis is markedly activated in SNI rats, thereby exacerbating neuroinflammation and mechanical allodynia. Importantly, ferroptosis suppresses the expression of α7nAChR, while ICTF interrupts this vicious cycle by upregulating α7nAChR, inhibiting ferroptosis-related iron accumulation, lipid peroxidation, and the downregulation of GPX4, ultimately alleviating SNI-induced neuropathic pain. This study offers a scientific interpretation of the traditional use of Epimedium-derived active compounds for treating neuropathic pain at the modern molecular mechanism level."

Journal • Hematological Disorders • Inflammation • Neuralgia • Pain • GPX4 • HMOX1 • SAT1

Injectable Thermosensitive Hydrogel Targeting STAT3 Reprograms Neutrophils to Amplify Anti-Tumor Immunity Post-Radiofrequency Ablation in HCC. (PubMed, Adv Healthc Mater) - "In vitro, icaritin (ICT) inhibits TAN survival and migration, and reverses the immunosuppressive phenotype by suppressing STAT3 phosphorylation...Multi-omics analyses reveal complementary mechanisms of ICT, which inhibits PD-L1 expression in TANs, disrupts TAN-tumor adhesion, and suppresses unsaturated fatty acid metabolism. Overall, with accessible materials and seamless integration with RFA, this strategy optimizes RFA efficacy, providing a safe and translational solution for HCC recurrence."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • STAT3

Icaritin plus TACE improves survival in advanced HCC with macrovascular invasion: a multicenter cohort study. (PubMed, Front Immunol) - "The overall incidence of any grade adverse events was similar between groups. Icaritin combined with TACE improves OS, PFS, and DCR compared to TACE alone in patients with MVI-associated HCC."

Journal • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP

Real-World Evidence on the Efficacy of Icaritin for Unresectable Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Study. (PubMed, Int J Cancer) - "Icaritin shows promising efficacy in unresectable HCC, particularly in patients with lower AFP levels. The findings support personalized treatment strategies and warrant further research to optimize outcomes and elucidate Icaritin's mechanisms."

HEOR • Journal • Real-world evidence • Retrospective data • Hepatocellular Cancer • Oncology • Solid Tumor • AFP

Design, synthesis, and biological evaluation of novel ICA-II derivatives as anti-hepatocellular carcinoma agents targeting EGFR. (PubMed, Eur J Med Chem) - "This molecule exhibited robust anti-proliferative activity across multiple HCC cell lines (HepG2, Hep3B, and Huh7), surpassing both the parent ICA-II and the positive control Sorafenib...Compound 3b administration markedly suppressed tumor growth without significant body weight loss or obvious histopathological abnormalities in major organs under the tested conditions, notably outperforming the clinically approved agent Icaritin. Preliminary pharmacokinetic studies further demonstrated that 3b achieved robust systemic exposure and a prolonged retention time following intravenous administration. Overall, our work provides a successful structural optimization rationale for ICA-II and advances 3b as a safe, EGFR-modulating lead compound for HCC intervention."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • EGFR

Metapath2vec and attention-driven heterogeneous graph learning for prioritizing TCM-derived small molecules in gastric cancer. (PubMed, Chin Med) - "Network pharmacology and in vitro validation in AGS and MKN-45 gastric cancer cell lines show that Icaritin and Arundine inhibit cell proliferation and induce apoptosis. This study presents an AI-assisted pipeline for candidate prioritization, providing methodological support for the systematic prioritization and preliminary validation of bioactive TCM molecules in gastric cancer."

Heterogeneity • Journal • Gastric Cancer • Oncology • Solid Tumor

Clinical and translational study of YBX1 as a biomarker and therapeutic target in bone metastasis of non–small cell lung cancer. (ASCO 2026) - "YBX1 is a promising prognostic biomarker and therapeutic target in NSCLC bone metastasis. Its upregulation drives immunosuppression and osteolytic progression, while targeting YBX1 glycosylation with Icaritin inhibits metastasis and synergizes with immunotherapy."

Biomarker • Clinical • IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8 • IL6 • YBX1

Efficacy and safety analysis of TACE combined with lenvatinib and icaritin in unresectable hepatocellular carcinoma with poor performance status. (PubMed, BMC Cancer) - "TACE combined with lenvatinib and icaritin demonstrates good efficacy and safety in the treatment of patients with uHCC and poor physical condition (ECOG = 2). This combination therapy may be a viable option for improving prognosis and quality of life in patients with uHCC and poor physical condition."

Journal • Anorexia • Dermatology • Fatigue • Hepatocellular Cancer • Oncology • Solid Tumor

Traditional Chinese Medicine Reverses Immune Checkpoint Resistance Through Lactate Metabolic Reprogramming in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications. (PubMed, J Ethnopharmacol) - P3 | "TCM-mediated lactate metabolic reprogramming is a biologically plausible strategy warranting further investigation for ICB-resistant HCC. The current evidence linking lactate to ICB resistance in human HCC remains largely supportive and correlative rather than definitively causal-several pivotal mechanistic findings derive from non-HCC models-and should be interpreted accordingly. Biomarker-enriched, pharmacokinetically informed TCM-ICB combination trials with direct intratumoural lactate measurement are required."

IO biomarker • Journal • Review • Hepatocellular Cancer • Liver Failure • Oncology • Solid Tumor • AMPK • CXCL9 • HIF1A • JAK2 • PD-L1 • STAT3

MMIP-assisted selective molecular depletion of icaritin-type aglycones for causality-guided metabolite identification in fermented Epimedium. (PubMed, J Chromatogr A) - "Selective removal of aglycones resulted in a pronounced attenuation of cartilage-promoting effects in zebrafish models, and the magnitude of functional loss was quantitatively correlated with the degree of depletion, providing direct evidence of metabolite-activity causality. Compared with conventional fractionation approaches, the proposed strategy enables selective chromatographic modulation of target analytes with minimal disturbance to the surrounding chemical matrix, extending chromatographic analysis from passive profiling to active molecular intervention and providing a generalizable framework for causality-oriented metabolite identification in complex systems."

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Boosting oral bioavailability of icaritin and piperine: A co-amorphous approach with molecular insights and performance validation. (PubMed, Drug Dev Ind Pharm) - "The system maintained excellent physical stability for six months under storage conditions. This study successfully developed a stable ICT-PIP co-amorphous system with superior solubility and bioavailability characteristics, demonstrating the effectiveness of co-amorphization as a viable strategy for optimizing the delivery of poorly soluble drug combinations."

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An integrative multi-modal computational framework identified hub prognostic targets and natural inhibitors for tobacco-specific nitrosamine-induced lung adenocarcinoma. (PubMed, Comput Biol Chem) - "Furthermore, eight lead compounds (resibufogenin, psoralidin, icaritin, ononin, salidroside, polydatin, hesperetin, and berberine hydrochloride) were screened as potential natural inhibitors. By elucidating the multi-target pathogenic role of TSNAs in LUAD from macro-epidemiology to molecular mechanisms, this study established an interpretable prognostic model for risk assessment and identified potential natural lead compounds for LUAD therapy."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GDF15 • S100P

The therapeutic potential of epimedium and its bioactive flavonoids in hepatitis and cirrhosis: an integrative review. (PubMed, Front Cell Infect Microbiol) - "Traditional Chinese medicine has long employed Epimedium species (Berberidaceae) for hepatoprotective indications, with contemporary investigations identifying prenylated flavonoids-principally icariin and its active metabolite icaritin-as the principal bioactive constituents...Epimedium flavonoids exhibit multi-target therapeutic potential that bridges traditional botanical medicine and modern pharmacology, though critical translational gaps persist. Future investigations must prioritize phase III fibrosis trials, pharmacokinetic optimization in cirrhotic populations, and comprehensive drug-drug interaction studies with direct-acting antivirals to establish evidence-based clinical protocols."

Journal • Review • Fibrosis • Hepatocellular Cancer • Hepatology • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • Solid Tumor • Transplantation • CD8 • HIF1A • KDR • TGFB1

Icaritin inhibits castration-resistant prostate cancer via RhoB-mediated Akt signaling. (PubMed, Pathol Res Pract) - "Subsequent mechanistic investigations revealed that icaritin inhibits CRPC progression by modulating RhoB-mediated Akt signaling. Collectively, these findings indicate that the anti-CRPC activity of icaritin is at least partially mediated through the RhoB/Akt signaling, providing a pharmacological basis for the further development of icaritin as a potential therapeutic agent against CRPC."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

Investigating the pharmacokinetics and conjugate metabolism of potential hepatotoxic prenylflavonoids in Epimedium extract using LC-MS/MS. (PubMed, J Pharm Biomed Anal) - "The results identify icaritin as the component with the highest systemic exposure and greatest potential for accumulation, suggesting it may be a candidate contributor to Epimedium-associated hepatotoxicity. These findings provide a pharmacokinetic foundation for future toxicological investigations."

Journal • PK/PD data