clodronate disodium
/ Generic mfg.
- LARVOL DELTA
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November 04, 2025
DYRK1A controls CD47 endocytic degradation and leukemia immune surveillance
(ASH 2025)
- "Importantly, pre-treatment of animals with clodronate liposomes to eliminatemacrophages revealed that macrophages are required for therapeutic efficacy of selective DYRK1Ainhibition.To understand the mechanism by which DYRK1A regulates CD47, we performed serine/threoninephosphoproteomics on MV4; 11 and THP-1 AML cells treated with SM13797...Genetic orpharmacologic inhibition of DYRK1A in AML disrupts DYRK1A-mediated phosphorylation of endocyticregulators such as CBL, thereby promoting CD47 endocytosis, reducing cell surface CD47 abundance,and enhancing macrophage-mediated phagocytosis. Finally, we identify a novel ultra-selective DYRK1Ainhibitor whose promising preclinical activity in AML harnesses innate immune recognition."
IO biomarker • CNS Disorders • Developmental Disorders • Diabetes • Genetic Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Targeted Protein Degradation • CD47 • DYRK1A • DYRK1B
November 04, 2025
High fructose diet exacerbates acute GVHD through microbiota dysbiosis and HIF-1α–mediated macrophage activation
(ASH 2025)
- "Macrophage depletion with clodronate liposomes and gut microbiota ablation by broad-spectrum antibiotics were employed to confirm their roles in HFR-exacerbated aGVHD.In this study, we demonstrate that mice fed HFR exhibited increased mortality, elevated aGVHD scores,and worsening histological damage in target organs... Taken together, our data indicate that high fructose intake aggravates aGVHD by disrupting gutmicrobiota and enhancing inflammatory macrophage responses. Our findings highlight dietary fructoserestriction as a potential approach for mitigating aGVHD."
Dysbiosis • Acute Graft versus Host Disease • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Inflammation • HIF1A • IL12A • IL1B • IL6 • TNFA
November 04, 2025
DNMT3A-driven clonal hematopoiesis permits colitis-associated tumorigenesis by promoting innate immune tolerance
(ASH 2025)
- "Indeed, myeloid-specific heterozygous Dnmt3a loss (by LysM-Cre) was sufficient to promote tumor initiation, whiledepletion of phagocytes in vivo using clodronate liposomes during CAC induction reversed Dnmt3a-CH-induced increase in colon tumor burden.In conclusion, DNMT3A-driven CH enables colitis-associated tumorigenesis by priming myelopoiesistowards innate immune tolerance under excessive inflammation, creating an immunosuppressive TMEand corrupting tumor control. Targeting innate immune tolerance in individuals with DNMT3A-CH mayrepresent a strategy to mitigate the risk of inflammation-associated cancers."
Colon Cancer • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • DNMT3A • IL10 • IL1B • PTPRC • TNFA
November 04, 2025
Fibroblast-activating protein as a biomarker for blood-induced joint inflammation in hemophilia
(ASH 2025)
- "To assess the effect of monocyte-derivedmacrophages (MDM) on the clearance of blood, we eliminated monocytes by injecting wildtype miceintravenously with 200 µL clodronate liposomes prior to the injection of anticoagulated blood into theright knee joint... We demonstrate that hemarthrosis in hemophilia represents a relevant inflammatorystimulus that leads to fibrotic joint degeneration. Blood-induced joint inflammation in hemophilia isamplified by impaired blood clearance and correlates strongly with FAP expression as well as IL-6upregulation. Based on these data, we propose to further investigate 68Ga-FAPI PET/CT Scans incombination with plasma IL-6 levels as biomarkers for acute blood-induced synovitis in hemophilia."
Biomarker • Fibrosis • Hematological Disorders • Hemophilia • Hemophilia A • Hemophilia B • Immunology • Inflammation • Inflammatory Arthritis • Osteoarthritis • Rare Diseases • Rheumatology • CD68 • FAP • IL1B • IL6 • TGFB1
November 04, 2025
Pharmacological targeting of CTPS1 elicits macrophage-mediated anti-leukemia immunity
(ASH 2025)
- "Macrophage depletion byliposomal clodronate before STP-B treatment completely abolished survival advantages seen in STP-B-treated mice...To investigate these activities, we reconstituted CTPS1-knockout THP-1 cells with wild-type or glutaminase-deficient mutant CTPS1. Relative to wild-type CTPS1,expression of the mutant form exhibited ISG upregulation, suggesting that deamidation activity is criticalto suppress IFN signaling.Together, these findings reveal that systemic STP-B treatment drives macrophage specification andinnate immune activation, highlighting STP-B as a leukemia-ablating agent with immune-stimulatorypotency."
IO biomarker • Acute Myelogenous Leukemia • Brain Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • CD14 • CD33 • CD34 • CD86 • CTPS1 • CXCL10 • CXCL9 • IL1A • IL6 • ITGAM • PTPRC
December 08, 2025
Engineering and evaluation of precision-glycosylated clickable albumin nanoplatform for targeting the tumor microenvironment.
(PubMed, Theranostics)
- "Clodronate-loaded glycosylated albumins were tested for tumor-associated macrophage (TAM) depletion...Integrating PET with ST provides a robust framework for mechanistic mapping of nanomedicine uptake. The CAN-DGIT platform offers a versatile strategy for developing targeted theranostic agents with immunomodulatory potential."
Biomarker • Journal • Oncology • MRC1 • SLC2A1
December 05, 2025
Sanzi Yangqin Decoction alleviated epithelial barrier damage in acute lung injury by mediating CD40 in alveolar macrophages to inhibit necroptosis of pulmonary epithelial cells.
(PubMed, Phytomedicine)
- "SZYQ improved epithelial barrier function in ALI by mediating the CD40 of AMs. Its mechanism of action involved inhibiting necroptosis in AT2, alleviating mitochondrial fission, and promoting the proliferation and differentiation of AT2."
IO biomarker • Journal • Acute Lung Injury • Inflammation • Pulmonary Disease • Respiratory Diseases • CD40 • CD40LG • RIPK1
December 01, 2025
Single-cell multiomics reveals macrophage-derived IL-23 and CXCL9/10 drive pathogenic IFNG+IL17+ T cells in immunotherapy-related colitis.
(PubMed, J Immunother Cancer)
- "IFNG+IL17+CD4+ T cells and CXCL9/10-producing macrophages are key mediators of irColitis. Targeting IL-23 signaling and intestinal macrophages represents a promising strategy to alleviate gut immunopathology without compromising the efficacy of ICB therapy."
Journal • Colorectal Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Oncology • Solid Tumor • CD4 • CXCL10 • CXCL9 • CXCR3 • IFNG • IL17A • IL23A
November 26, 2025
EXPRESS: Evodiamine attenuates chemotherapy-induced peripheral neuropathy by mediating macrophage M2 polarization and inhibiting the upregulation of the p38 MAPK-TRPV1 axis in rat dorsal root ganglia.
(PubMed, Mol Pain)
- "Evodiamine alleviates CIPN through a novel neuroimmune mechanism involving M2 macrophage polarization and inhibition of the p38/MAPK-TRPV1 axis in DRG neurons. These findings establish macrophage polarization as a key therapeutic target and highlight evodiamine's potential as a natural therapeutic agent for CIPN management."
Journal • Preclinical • Neuralgia • Pain • Peripheral Neuropathic Pain • CD163 • CD86 • IL1B • IL6 • MRC1 • TNFA • TRPV1
November 25, 2025
A genome-wide CRISPR screen in Anopheles mosquito cells identifies fitness and immune cell function-related genes.
(PubMed, Nat Commun)
- "For the latter, we confirm roles in liposome uptake and processing through in vivo validation in Anopheles gambiae that provide new mechanistic detail of phagolysosome formation and clodronate liposome processing. Altogether, we present a genome-wide CRISPR knockout platform in a major malaria vector and identify genes important for fitness and immune-related processes."
Journal • Infectious Disease • Malaria
November 24, 2025
Neural Inflammation in Thoracic Dorsal Root Ganglia Mediates Cardiopulmonary Spinal Afferent Sensitization in Chronic Heart Failure.
(PubMed, bioRxiv)
- "Targeting DRG inflammation, particularly with sustained local dexamethasone delivery using ProGel-Dex, offers a precision medicine to dampen pathological sympathetic activation and improve cardiac outcomes in CHF. Both cardiac (CSAR) and pulmonary (PSAR) spinal afferent reflexes are sensitized after myocardial infarction, contributing to sympathetic overactivation.Thoracic dorsal root ganglia (T1-T4) exhibit macrophage activation, glial responses, pro- inflammatory cytokine upregulation, and suppression of Kv channels following MI.Cardiac afferents mediate receptor-dependent uptake and transport of cytokines (e.g., TNF-α) from the heart to DRGs, driving macrophage infiltration and inflammation.Activated macrophages and pro-inflammatory cytokines reduce Kv channel expression and Kv current density (Ito) in DRG neurons, enhancing excitability.Anti-inflammatory strategies including minocycline, liposomal clodronate-induced macrophage depletion, and local epidural..."
Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • Myocardial Infarction • TNFA
November 18, 2025
Antiosteolytic Bisphosphonate Metallodrug Coordination Networks: Dissolution Profiles and In Vitro/In Vivo Toxicity toward Controlled Release.
(PubMed, ACS Appl Bio Mater)
- "Coordination compounds were synthesized and structurally characterized containing biocompatible alkaline earth metal ions and the bone-seeking agents clodronate (CLOD, (dichloromethanediyl)bis(phosphonate)) and medronate (MED, methylenediphosphonate)...The overall drug release profile for each system was the result of several structural factors, such as H-bonding interactions, strength of the metal-O(phosphonate) bonds, and packing density, but also crystal morphological/textural factors. These compounds were also tested for their toxicity at the concentration of 100 μM in vitro (micronucleus assay) and in vivo (brine shrimp Artemia salina) and were found to be of low toxicity."
Journal • Preclinical • Osteoporosis • Rheumatology
October 07, 2025
Perivascular Macrophages Mediate Vascular Dysfunction and Cerebral Amyloid Angiopathy in Alzheimer's Disease Models
(Neuroscience 2025)
- "To investigate the role of PVMs in vascular damage, we will employ clodronate liposome-mediated macrophage depletion, assessing its effects on both amyloid deposition and cerebrovascular health... This study will provide important insights into the role of PVMs in mediating vascular dysfunction and CAA in AD. By elucidating the mechanisms through which PVMs contribute to cerebrovascular pathology, our findings could inform new therapeutic strategies targeting both amyloid clearance and vascular protection in AD and other neurodegenerative diseases characterized by neuroimmune-vascular interactions."
Alzheimer's Disease • CNS Disorders
October 07, 2025
Microglia are necessary for retention of a unique and transient mast cell population in the developing brain.
(Neuroscience 2025)
- "Compelling new data indicate that experimental depletion of microglia at PN0 and PN1 using clodronate liposomes (clodronate) leads to a persistent decrease in phMC numbers throughout the first two postnatal weeks compared to empty liposome treated controls (vehicle)...We expect to observe an increase in MCs in these tissues when microglia are depleted, suggesting that microglia are secreting a factor that either recruits or encourages residency of the MCs in this peri-hippocampal space. If confirmed, this would be a novel interaction between microglia and canonical peripheral immune cells in early postnatal development with implications for brain health and disease."
Clinical • CNS Disorders
November 15, 2025
TAMs-mediated resistance to oncolytic virus M1 in solid tumors.
(PubMed, J Immunother Cancer)
- "TAMs, particularly M1-like subsets, play a critical role in mediating resistance to OVM therapy by reducing viral persistence and suppressing CD8+ T-cell responses. Targeting TAMs significantly improves the antitumor efficacy of OVM in solid tumors. These findings support the development of TAMs-targeted combination strategies to optimize oncolytic virotherapy."
Journal • Colorectal Cancer • Genito-urinary Cancer • Melanoma • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • CD8 • CSF1R • GZMB
November 06, 2024
Infiltration of Innate Immune Cells into Tumors By Polatuzumab Vedotin Treatment Contributes to Its Antitumor Effect in Xenograft and Syngeneic Mouse Models
(ASH 2024)
- "In these models, human IgG or Pola (2–5 mg/kg) was injected intravenously on day 1, and clodronate liposomes or anti-asialo GM1 (reagents that deplete MΦ and NK cells, respectively) was injected regularly from day 0. Moreover, innate immune cells also contributed to the antitumor effect of Pola in the syngeneic mouse model. Differences in the status of innate immune cells in the tumor microenvironment could affect the efficacy of Pola."
Immune cell • Preclinical • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CALR • CD79B • GZMB • HMGB1 • PTPRC
November 03, 2023
H2-K1 on MLL-AF9 Leukemia Cells Facilitates the Escape of NK Cell-Mediated Immune Surveillance
(ASH 2023)
- "Macrophage depletion by clodronate liposomes did not affect the in vivo expansion of H2-K1 sgRNA-expressing leukemia cells demonstrating that macrophages were not suppressed by H2-K1 on the leukemia cells...H2-K1 alters the maturation and activation of NK cells in the bone marrow niche. These findings increase our understanding of how leukemia cells escape immune surveillance and suggest that the identification of corresponding mechanisms in human AML could pave the way for new therapies that boost the endogenous NK cells by restoring immune surveillance mechanisms."
IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD27 • ITGAM • KIT • NKG2D
November 13, 2025
Transient Osteoporosis of the Hip: Clinical and Radiological Outcomes After Combined Pharmacologic and Biophysical Therapy.
(PubMed, J Clin Med)
- "The aim of this study was to evaluate clinical outcomes following treatment with Neridronate, Clodronic Acid, Cholecalciferol, and pulsed electromagnetic field therapy (PEMF). Early diagnosis and timely intervention are essential to progression to osteonecrosis. A combined therapeutic approach using bisphosphonates, vitamin D, and PEMF appears effective in reducing symptoms, promoting bone healing, and ensuring good patient compliance."
Journal • Immunology • Osteoporosis • Pain • Rheumatology
November 13, 2025
Effects of clodronate disodium on markers of inflammation and cartilage metabolism in juvenile horses challenged with intra-articular lipopolysaccharide.
(PubMed, J Anim Sci)
- "There was a treatment × time × carpus interaction (P = 0.02) in which 1X, 2X and 4X CD groups had greater synovial PGE2 concentrations at 6 h post-injection in the LPS joint compared to 0X. The results of this study indicate that administration of CD increases intra-articular inflammation (PGE2) but does not affect cartilage degradation (C2C) and only tends to increase cartilage synthesis (CPII) according to biomarkers measured."
Journal • Inflammation
October 18, 2025
Circadian Bmal1/Rev-erbα/CSF-1 Axis in Proximal Tubules Modulates Macrophage-Driven Diurnal Variation in Renal Ischemia-Reperfusion Injury
(KIDNEY WEEK 2025)
- "Macrophage depletion via clodronate liposomes similarly eliminated the diurnal variation of RIRI and significantly attenuated renal damage specifically at ZT12...Conclusion Our findings reveal a circadian Bmal1–Rev-erbα–CSF-1 axis in proximal tubules that governs the rhythmic infiltration of macrophages and drives diurnal variation in RIRI severity. Targeting this pathway may offer novel chronotherapeutic strategies for the prevention and treatment of RIRI."
Acute Kidney Injury • Cardiovascular • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • ARNTL • BMAL1 • CSF1 • CSF1R • NR1D1
November 06, 2024
Low Dose Clodronate Improves Exercise Tolerance, Right Ventricular Function, and Alters Resident Lung Macrophage Phenotypes
(ASH 2024)
- "When metabolomics were analyzed, the urea cycle was significantly increased in Berk Hx Tx compared to Berk Hx. Together, these data show that low dose of clodronate in a SCD-PH mouse model alter phenotypes at both the whole organ and cellular (Mf) levels to slow progression of PH and increase exercise tolerance."
Cardiovascular • Genetic Disorders • Hematological Disorders • Inflammation • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Sickle Cell Disease
November 06, 2024
Patient-Derived Models of Clonal Hematopoiesis Point to Cell-Intrinsic and -Extrinsic Contributions to Clonal Dominance and Lineage Imbalances
(ASH 2024)
- "We engrafted DNMT3A CH-CD34+ into clodronate/busulfan-conditioned NSG mice. These findings suggest that clonal fitness and the differentiation imbalances of DNMT3A CH CD34+ cells are, at least partially, driven by intrinsic factors. In conclusion, our findings from scRNAseq analysis, in vitro and in vivo models of human-derived CH point towards both cell-intrinsic and cell-extrinsic factors that contribute to clonal behavior and lineage imbalances."
Clinical • IO biomarker • Hematological Disorders • Inflammation • ASXL1 • CD34 • CD38 • CXCL12 • DNMT3A • GYPA • JUN • MME • PTPRC • SLAMF7 • TET2 • TFRC
November 06, 2024
Alpha 2-Adrenergic Agonist As a Novel Microenvironment-Directed Agent for Acute Myeloid Leukemia Via Notch Signaling Inhibition
(ASH 2024)
- "Methods : To evaluate whether the α2-AR agonist (clonidine, CLD) could be a novel agent for AML, we utilized MLL-AF9+ AML model mice...Furthermore, the anti-tumor effect was not attenuated by depletion of BM macrophages with clodronate liposomes, and no synergistic effect of CLD with anti-PD-1 antibody was observed, as previously reported in solid tumors...This suppression contributes to a reduction in AML progression and improvement in survival. These results suggest that α2-AR agonists hold potential as novel therapeutic agents for AML and warrants further investigation for clinical application."
IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Solid Tumor • GAPDH • HES1 • JAG1 • NOTCH1 • NOTCH2
November 06, 2024
Reconstruction of Megaloblastic Anemia in a Novel Erythroblastic Island Humanized Mouse Model with Mature Circulating Human Red Blood Cells
(ASH 2024)
- "Administration of clodronate liposome (Clod) abrogates murine macrophages and rescues circulating peripheral blood (PB) hRBCs in HIS mice, but only transiently and with significant toxicity...We used a combination of anti-mouse CSF1R and F4/80 antibodies with dexamethasone for repopulating human EBIs in HIS mice (EBI-HIS)...In summary, we herein present our EBI-HIS mice with enhanced human erythropoiesis and circulating fully mature hRBCs. This improved human RBC model recapitulated clinical features of life-threatening erythropoietic disorders like hereditary MgA, and could serve as a valuable preclinical animal model for development and evaluation of therapeutics."
Preclinical • Anemia • Cardiovascular • Hematological Disorders • Thrombosis • CD14 • CD163 • CSF1R • GYPA • TFRC
November 06, 2024
Liver and Spleen Work Together to Clear Allogeneic Platelets from the Bloodstream during Transfusion Refractoriness
(ASH 2024)
- "The role of the liver was assessed by administering a low dose of clodronate liposomes (6.5 mg/kg i.v.) 24 h before transfusion...Although the mechanisms by which these platelets are eliminated remain unclear, they do not seem to depend on asialoglycoprotein receptors, nor FcγR. This suggests there is an alternative or a compensatory mechanism, which sets apart this platelet elimination from other immune platelet pathologies."
ASGR • CD31 • ITGAM • PECAM1 • PTPRC
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