vadimezan (ASA404) / Antisoma - LARVOL DELTA

DMXAA accelerates orthodontic tooth movement via macrophage-mediated Rab13-enriched extracellular vesicle release and chemokine secretion. (PubMed, Prog Orthod) - "DMXAA accelerates OTM through a dual mechanism: chemokine-driven osteoclast differentiation and sEV-Rab13-mediated osteoclast fusion. These findings highlight the Rab13-sEV axis as a novel therapeutic target for modulating the periodontal microenvironment and enhancing orthodontic efficiency. Our results elucidated a novel mechanism by which DMXAA accelerated orthodontic tooth movement and suggested it as a potential therapeutic agent to optimize orthodontic treatment."

Journal • CXCL10 • RAB13

Nobiletin attenuates LPS-induced acute lung injury via a STING-dependent signaling pathway. (PubMed, Arch Pharm Res) - "Functional validation was conducted using the STING agonist vadimezan (DMXAA), the STING inhibitor SN-001, and STING-knockout (STING-KO) mice...Moreover, in STING‑KO mice with LPS‑induced ALI, the loss of the protective effect of Nob further confirmed that its anti‑inflammatory activity depends on STING, highlighting the essential role of STING signaling in mediating its protective effects. In conclusion, the protective effect of Nob on an LPS-induced ALI model is mediated primarily through the modulation of STING signaling."

Journal • Acute Lung Injury • Inflammation • Pneumonia • Respiratory Diseases • STING

rhFGF21-loaded P hydrogel promoted diabetic wound repair by regulating the inflammatory cytokine expression and phagocytic function of macrophages via the STING-mediated autophagy pathway. (PubMed, Int Immunopharmacol) - "Furthermore, rhFGF21 increased the expression of LC3II protein, inhibited the mRNA levels of inflammatory cytokines (TNF-α and IL-6) and enhanced phagocytosis in HG + LPS-treated MPMs, but these effects were reversed by the STING agonist Vadimezan. These results demonstrated that rhFGF21-P promoted diabetic wound healing through inhibiting the expression of inflammatory cytokines and enhancing phagocytic function of macrophages via the modulation of STING-mediated autophagy."

Journal • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • FGF21 • IL6 • MIP-2 • STING • TNFA

Tumor/Lymph Node Dual-Targeting Ultrasonic Nanoconverter Orchestrates Spatiotemporal ROS Regulation for Dual-Zone Programmed Sono-STING Immunotherapy. (PubMed, Small) - "Herein, a dual-targeting ultrasonic nanoconverter (OPD@PSF) is elaborately engineered through in situ polymerization to co-deliver a sonosensitizer protoporphyrin IX (PpIX) and a stimulator of interferon genes (STING) agonist Vadimezan (DMXAA) to achieve dual-zone programmed sono-STING immunotherapy (DPSSI) in tumors and tdLNs...Additionally, DMXAA-mediated STING activation stimulates antigen-presenting cells, acting synergistically with ROS-driven SDT to eradicate primary tumors and suppress metastatic dissemination. By optimizing the US parameters, the rationally designed OPD@PSF exemplifies a new nanotechnological strategy for synergistic breast cancer therapy and metastasis suppression via tumor/tdLN dual-targeted delivery and systemic immune orchestration, holding great promise for clinical translation."

Journal • Breast Cancer • Oncology • Solid Tumor • STING

Mannosylated graphene oxide nanotherapeutics co-delivering docetaxel and a STING agonist reprogram myeloid cells and potentiate antitumor immunity. (PubMed, Mater Today Bio) - "Docetaxel and vadimezan (DMXAA), a prototypical STING agonist, were co-loaded into GO-EDM to generate GO-EDM-DTX-Vad. Taken together, GO-EDM-DTX-Vad leverages passive tumor accumulation and mannose receptor-guided dual targeting of TAMs and TIDCs to integrate DTX-based chemotherapy, STING-mediated immune activation and mild NIR photothermal therapy. This integrated chemo-photothermal-immunotherapeutic design couples direct tumor cell killing with myeloid reprogramming and immune activation, offering a unified strategy for metastatic TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

Engineering cell membrane nanoparticlesenhance immunotherapy and radiodynamic therapy for lung adenocarcinoma by promoting cGAS-STING and ferroptosis (AACR 2024) - "The vehicle utilized lung adenocarcinoma cell membranes as the outer shell and encapsulated iron-platinum nanoparticles and STING agonist Vadimezan... This study developed a targeted drug delivery strategy, FP/Vad@CC-aT2, to improve the tumor microenvironment (TME). We conducted preliminary experiments in vitro and in vivo to validate its physicochemical properties and tumor inhibitory effects, including the induction of ferroptosis. We assessed its safety in mouse and obtained initial evidence of FP/Vad@CC-aT2's ability to remodel the subtypes of macrophage.Moving forward, we will validate its therapeutic and impact on the TME after surgical procedures."

Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MRC1 • STING

Mitochondria-dependent STING activation enhances immune remodeling and cabozantinib response in hepatocellular carcinoma (LCS 2026) - "In vivo, cabozantinib reduced tumor growth and promoted CD8⁺ T cell and NK cell infiltration, which were further enhanced by vadimezan co-treatment...Conclusion Cabozantinib induces immune response depends on mitochondrial disruption and cGAS/STING activation, leading to immune remodeling in HCC. These findings provide insights into the immunomodulatory effects of cabozantinib, support combinations with STING agonists for treatment and suggest candidate biomarkers for predicting therapeutic response in TKI-treated patients."

Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • ANGPT1 • CA9 • CD8 • CXCL13 • GZMB • KDR • STING

Design, synthesis, and antitumor mechanism investigation of iridium(III)/ruthenium(II)-vadimezan conjugates towards 4T1 cells. (PubMed, J Inorg Biochem) - "Furthermore, Ir-VDA-1-3 functioned as the immunogenic cell death (ICD) inducers, promoting damage-associated molecular patterns (DAMPs) release, including calreticulin (CRT), high mobility group protein 1 (HMGB1), and adenosine triphosphate (ATP). This strategy provides a novel design concept for multimodal synergistic cancer therapy."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CALR • CASP3 • CGAS • GSDME • HMGB1 • STING

Effect of Corona Block Structure on Telodendrimer Micelles: Probing Exchange Kinetics by Fluorescence Spectroscopy. (PubMed, Biomacromolecules) - "Telodendrimer micelles with low critical micelle concentrations (CMCs) were synthesized using a hydrophilic poly(sarcosine) (PSar) block and a lysine-based dendritic block carrying four stably conjugated Vadimezan...Slower unimer re-entry was observed for larger, sterically hindered unimers. The study suggests that hydrophilic block size and topology are equally important in the design criteria as the hydrophobic portion for stability and CMC alone is insufficient to predict micelle behavior in complex biological media."

Journal

Anti-Triggering Receptor Expressed on Myeloid Cells 2-Conjugated Nanovesicles Loaded Vadimezan Reprogram Tumor-Associated Macrophages to Combat Recurrent Lung Cancer. (PubMed, ACS Nano) - "Simultaneously, anti-TREM2 effectively repolarized TAMs into M1-type macrophages, thereby reversing immunosuppressive TME together with a Vad-activated STING pathway, which promoted the maturation of dendritic cells and enhanced the infiltration of cytotoxic T lymphocytes. Therefore, this study highlighted the FP/Vad@CC-aT2-mediated cascade immune response for suppressing lung cancer recurrence that involves ferroptosis potentiation, TAM repolarization, and STING pathway activation."

Journal • Lung Cancer • Oncology • Solid Tumor • CGAS • STING

Acoustically activated nanoplatforms achieve tumor regression by exacerbating tumor hypoxia. (PubMed, J Cancer Res Ther) - "The DIS NPs exhibit a promising approach for hypoxia-exacerbated cancer starvation therapy, providing a potential new avenue for cancer treatment with demonstrated efficacy and biocompatibility."

Journal • Oncology

Implantable Biophotonic Device for Wirelessly Cancer Real-Time Monitoring and Modulable Treatment. (PubMed, Adv Sci (Weinh)) - "Furthermore, this device can also evaluate the therapeutic progression of chemotherapy drugs like vadimezan, which reduces sO2 levels by disrupting tumor angiogenesis...It operates via wireless power and data transmission without disrupting normal physiological activities. Hence, the biophotonic device is capable of concurrently achieving precise tumor discrimination, modulable in situ treatments, and real-time progression monitoring, enabling the evaluation and optimization of therapeutic efficacy."

Journal • Oncology

STING-activating layered double hydroxide nano-adjuvants for enhanced cancer immunotherapy. (PubMed, Biomaterials) - "Additionally, combining MLMF with the vascular disrupting agent Vadimezan disrupted the tumor's central region, typically resistant to immune cell infiltration, further extending survival in tumor-bearing mice. This innovative strategy may show great potential for improving cancer immunotherapy and offers hope for more effective treatments in the future."

Journal • Oncology • STING

A stimuli-responsive immunostimulant to activate chemo-immunotherapeutic effects by inducing DNA damage and STING activation. (PubMed, J Colloid Interface Sci) - "The MV@Lip system encapsulates the chemotherapeutic agent mitoxantrone (Mit) and the STING agonist vadimezan (Vad) within a redox-responsive liposomal carrier. This concerted action facilitates the infiltration and activation of natural killer (NK) cells and T lymphocytes in the tumor microenvironment, ultimately leading to the suppression of both primary and metastatic tumors. These findings provide a compelling basis for advancing chemotherapeutic combinations as immune-stimulating strategies in the treatment of metastatic malignancies."

Journal • Oncology • STING

Cabozantinib-Induced Mitochondrial Activation of the cGAS-STING Pathway Enhances the Antitumor Immunity in Experimental Hepatocellular Carcinoma (LCS 2025) - "In vivo, the anti-tumor efficacy of cabozantinib and/or vadimezan, a STING agonist, was evaluated using a subcutaneous Hepa1-6 injection mouse model... Cabozantinib induces mtDNA-dependent cell death via cGAS-STING signalling in hepatoma cells. STING stimulation enhanced cabozantinib efficacy. Our results, emphasize the role of the cGAS-STING axis in TKI therapies and its agonism as a promising strategy for HCC treatment."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • CD8 • CGAS • GZMB

A responsive cocktail nano-strategy breaking the immune excluded state enhances immunotherapy for triple negative breast cancer. (PubMed, Nanoscale) - "Herein, we fabricated a smart-responsive nanosystem (B&V@ZB-MCL) by integrating the extracellular matrix (ECM)-degrading drug losartan with a STING agonist (Vadimezan, abbreviated to Vad) and a PD-L1 inhibitor (BMS-1). The released Vad and damaged tumor DNA activated immune responses through the cGAS-STING pathway, while the elevated expression level of PD-L1 promoted the anti-tumor effect of BMS-1. Significant degradation of collagen fibers, restoration of immune effector cells, and lower tumor volume were observed in this integrated triple drug sequential therapy, which provides a promising prospect for TNBC treatment."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CGAS • STING

Multifunctional nanoparticles potentiate in-situ tumor vaccines via reversing insufficient Photothermal therapy by disrupting tumor vasculature. (PubMed, J Control Release) - "To overcome these limitations, we developed multi-functional nanoparticles (VI@Gd-NPs) that integrate a tumor vasculature-specific disrupting agent (Vadimezan, Phase III clinical drug), a photosensitizer (Indocyanine Green, ICG), and a magnetic resonance imaging contrast agent (Gadolinium, Gd) through chemical self-assembly...Moreover, depleting CD8+ T cells reverses these therapeutic benefits, highlighting the critical role of adaptive T cell immunity. Therefore, the VI@Gd-NPs treatment holds great potential for reigniting the in-situ tumor vaccine of photothermal therapy."

Journal • Oncology • CD8

Augmenting Post-Surgical Tumor Immune Response and Recurrence Prevention via Nanoparticle-Assisted Targeted Drug Delivery (IASLC-WCLC 2024) - "Methods : FP/Vad@CC-aT2, a biomimetic nanoparticle system containing FePt and Vadimezan, was prepared via extrusion and conjugated with anti-Trem2 antibodies...Conclusions : The study developed FP/Vad@CC-aT2, a targeted delivery system with good biocompatibility and significant antitumor effects. It was found to promote immune remodeling, induce immunogenic cell death, and alter immune cell composition in post-surgical relapse mouse models, suggesting its potential in preventing postoperative relapse and providing a basis for clinical applications."

IO biomarker • Lung Cancer • Oncology • Solid Tumor • CD8 • HMGB1 • STING

Identification of critical genes and metabolic pathways in rheumatoid arthritis and osteoporosis toward drug repurposing. (PubMed, Comput Biol Med) - "The results of the present study can provide novel insights into the pathogenesis and treatment of RA and OP."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Osteoporosis • Rheumatoid Arthritis • Rheumatology • CCL2 • HIF1A • IL10 • IL1B • IL6 • MMP9 • STAT3 • TGFB1 • TP53

Cabozantinib induces mtDNA-dependent cytotoxicity through cGas-STING signaling in experimental hepatocellular carcinoma (EASL-ILC 2024) - "Previous studies demonstrated that TKI inhibitors such as sorafenib and regorafenib induce mitochondrial damage during cancer treatment...Importantly, while blockage of this pathway (H-151) partially diminished cabozantinib cytotoxicity, vadimezan induction of cGas-STING potentiated the anti-tumor effect in vitro and in a Hepa1-6 3D spheroid model. Cabozantinib-induced mtDNA leakage to the cytosol induces ISGs signaling by activating the cGas-STING pathway in hepatoma cells. Our results reveal mitochondrial damage and the mtDNA-cGas-STING axis as compelling targets in antitumor efficacy with a potential role in immunological responses."

Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Oncology • Solid Tumor • CGAS • STING

Integrated anti-vascular and immune-chemotherapy for colorectal carcinoma using a pH-responsive polymeric delivery system. (PubMed, J Control Release) - "Herein, we designed a pH-responsive polymer to efficiently encapsulate a stimulator of interferon genes (STING) agonist (5,6- dimethylxanthenone-4-acetic acid, termed ASA404) and a common clinically used chemotherapeutic agent (1-hexylcarbamoyl-5-fluorouracil, termed HCFU). Histological analysis of the tumor micro-vessel density and enzyme-linked immunosorbent assay (ELISA) tests indicated that the system increased TNF-α and IFN-β levels in serum. Therefore, this research introduces a pH-responsive polymer-based theranostic platform with great potential for immune-chemotherapeutic and anti-vascular combination therapy of CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • IFNB1 • STING • TNFA

Computational study of small molecules with open and closed states of human STING: Effects on protein conformations and binding free energies (ACS-Fall 2023) - "An antitumor agent called DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan), which mimics the structure of cGAMP, was found to be very effective in murine models...The information gathered from this research further clarifies previous studies and proposed hypotheses, increasing our knowledge of the STING signaling pathway. They should assist in further designing the ligands as STING modulators and provide a theoretical basis for molecular-level understandings of their binding process to the STING proteins."

Oncology • STING

Radiation and STING activation limit tumor development and modulate the immune environment via distinct mechanisms (AACR 2023) - "In this study, we examined the effect of radiation and the STING agonist, DMXAA (Vadimezan), on the development of urethane-induced lung cancer.A/J mice were treated with urethane (i.p.) to induce the development of lung tumors...The different outcomes of RT and DMXAA on tumor growth may be driven by their distinctive mechanism of action on immune responses and capacities to form TLSs. These findings may have future implications for strategies for the early treatment of lung and other cancers, and they suggest that immune responses, including modulation of the STING pathway, may be an important aspect of early tumor development that could be targeted therapeutically."

Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCL13 • STING • TNFA

Nanodroplet-enhanced sonodynamic therapy potentiates immune checkpoint blockade for systemic suppression of triple-negative breast cancer. (PubMed, Acta Biomater) - "The synthesized nanodroplet consisted of a O-filled Perfluorohexane (PFH) core and a lipid membrane carrying sonosensitizer IR-780 and STING agonist Vadimezan (DMXAAs)...However, the hypoxic tumor microenvironment severely restricts the therapeutic efficiency of SDT, wherein, oxygen is indispensable in the process of ROS generation. Here, we report an O-filled nanodroplet-enhanced sonodynamic therapy that significantly potentiated immune checkpoint blockade for systemic suppression of TNBC."

Checkpoint inhibition • Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer

Lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein for combinational immunochemotherapy of metastatic triple-negative breast cancer. (PubMed, Acta Pharm Sin B) - "The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC."

Journal • Breast Cancer • Immune Modulation • Immunology • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1 • STING