Bindarit (AF 2838) / Angelini Group - LARVOL DELTA

CCL7-CCR3 signaling mediates olfactory dysfunction in a mouse model of allergic rhinitis. (PubMed, Front Immunol) - "The therapeutic efficacy of intranasal CCL7 inhibition was assessed using Bindarit over a sustained intervention period...In vitro, allergen-stimulated nasal epithelial cells secreted CCL7 that activated microglial cells through CCR3, an effect partially reversed by CCR3 antagonist. The CCL7-CCR3 signaling axis links nasal allergic inflammation to OB microglial neuroinflammation and consequent OD in AR, identifying a promising therapeutic target for AR-associated OD."

Journal • Preclinical • Allergic Rhinitis • Immunology • Inflammation • CCL7 • CCR3

Roles of CCL2 in peri-implantitis and its potential as a treatment target: An animal study. (PubMed, J Periodontol) - "Peri-implantitis, an inflammatory condition that impacts the longevity of dental implants, poses considerable challenges due to the limited effectiveness of current treatment methods. This study aimed to understand the role of CC-chemokine ligand 2 (CCL2) in this condition. In our study, CCL2 was discovered to be the primary ligand of CC-chemokine receptor 2 in peri-implantitis. Lab tests using a mouse model revealed that in the absence of CCL2, inflammation and bone loss were reduced. Furthermore, this study confirmed the effect of a drug called bindarit, which inhibits CCL2, in treating experimental peri-implantitis. Investigating the specific roles of CCL2 and assessing the potential benefits of bindarit in managing peri-implantitis provide a scientific foundation for exploring new treatment strategies."

IO biomarker • Journal • Inflammation • Mucositis • Osteoporosis • CCL2 • IL1B • IL6 • ITGAM • PTPRC • TNFA • TRAP

Time-Course Transcriptomic Analysis Reveals PANoptosis-CCL2 Axis in Herpes Simplex Keratitis. (PubMed, Invest Ophthalmol Vis Sci) - "The PANoptosis-CCL2/C-C motif chemokine receptor 2 (CCR2) axis was significantly upregulated in infected corneas and could be suppressed by a PANoptosis inhibitor or the CCL2 antagonist Bindarit. This study demonstrated the temporal coordination between immune activation and PANoptosis in HSK, highlighting PANoptosis as a crucial mechanism in amplifying antiviral immune responses. The ZBP1-PANoptosome-mediated PANoptosis-CCL2/CCR2 axis represents a potential therapeutic target for modulating the immune responses in HSK."

Journal • Herpes Simplex • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology • CCL2 • CCR2 • HLA-DRB1 • IFNB1 • IGF2BP1 • ZBP1

Bindarit attenuates brain injury and neuroinflammation in status epilepticus by disrupting C3/C3aR signaling and modulating microglia-astrocyte interactions. (PubMed, Cell Commun Signal) - No abstract available

Journal • CNS Disorders • Epilepsy • Inflammation • Vascular Neurology

tPLGA nanoparticles combined with CCL2/CCR2 inhibitor mitigate post-thrombolytic hemorrhagic transformation. (PubMed, Biomater Sci) - "When combined with Bindarit, an inhibitor of the CCL2/CCR2 pathway, this strategy achieves both targeted thrombolysis and effective suppression of HT...Behavioral, histological, and biosafety assessments confirmed improved neurological recovery and translational potential. This work establishes a therapeutic platform integrating precision thrombolysis with immune modulation for a safer and more effective treatment of ischemic stroke."

Journal • Cardiovascular • Hematological Disorders • Immune Modulation • Immunology • Ischemic stroke • Thrombosis • CCL2 • CCR2 • MMP9

Tet2 deficiency-induced expansion of monocyte-derived macrophages promotes liver fibrosis. (PubMed, J Exp Med) - "Pharmacological inhibition of Ccl2/Ccl8 with Bindarit attenuated MDMs accumulation and liver fibrosis, whereas combined therapy with Bindarit and IL-6 neutralization synergistically suppressed liver fibrosis in Tet2ΔMye mice and aged chimeric models recapitulating Tet2ΔMye-related myeloid hematopoiesis. These findings present the mechanism that Tet2ΔMye aggravates liver fibrosis and highlight MDMs depletion plus IL-6 neutralization as a promising therapy for liver fibrosis in patients with Tet2ΔMye-related myeloid hematopoiesis."

Journal • Fibrosis • Hematological Disorders • Immunology • Liver Cirrhosis • CCL2 • CCL8 • CCR2 • IL6 • TET2

Suppression of microglial activation with anti-inflammatory drug bindarit enhances neural development in the shunt-treated neonatal hydrocephalus model rat. (PubMed, Exp Neurol) - "These findings suggest that adjunctive anti-inflammatory therapy with bindarit enhances the neuroprotective effects of CSF diversion surgery by mitigating microglial activation and promoting oligodendrocyte maturation and myelination. This combined approach may offer a promising strategy for supporting brain development and improving neurocognitive outcomes in neonatal hydrocephalus."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Inflammation • Solid Tumor • Ventriculomegaly • CCL2 • CD68 • MBP

Bindarit-loaded hydrogel sustained-release system alleviates periodontitis in mice via CC motif chemokine ligand 2-dependent monocyte chemotaxis. (PubMed, J Control Release) - "All these effects were reversed by CCL2 overexpression, confirming a CCL2-dependent mechanism. This study establishes a promising immunomodulatory strategy for periodontitis, highlighting the potential of sustained-release hydrogels in treating inflammatory diseases."

Journal • Preclinical • Dental Disorders • Immune Modulation • Immunology • Inflammation • Osteoporosis • Periodontitis • CCL2

Wogonin modulates macrophage polarization and inflammatory signaling through the LSD1-p65 axis to alleviate osteoarthritis. (PubMed, Phytomedicine) - "Wogonin alleviates OA pathology by targeting the LSD1-p65 axis to balance macrophage polarization and mitigate inflammatory cascades. Its dual modulation of immune responses and tissue repair highlights therapeutic potential, warranting validation in large animal models and human OA tissues for clinical translation. This work positions wogonin as a novel disease-modifying agent for OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • CCL2 • CD163 • IL6 • KDM1A • NFKBIA • TNFA

Endothelial PRMT7 prevents dysfunction, promotes revascularization and enhances cardiac recovery post-myocardial infarction. (PubMed, Exp Mol Med) - "Conversely, PRMT7 overexpression or treatment with the PRMT7-inducing drug bindarit restores EC function, suppresses ER stress and enhances revascularization and cardiac repair after MI. These findings establish endothelial PRMT7 as a critical regulator of EC survival and function, highlighting its potential as a therapeutic target to mitigate ER stress and improve post-MI cardiac recovery."

Journal • Cardiovascular • Fibrosis • Immunology • Myocardial Infarction • Oncology • PRMT7 • TNFA

Mesenchymal stromal cells highly expressing Sca-1 promote breast cancer lung metastasis through recruiting myeloid cells. (PubMed, Cell Death Dis) - "Inhibition of macrophage chemotaxis by Bindarit, an inhibitor of CCL2/7/8 transcription, decreased the lung tumor burden induced by Sca-1high MSCs. Using Ccr5-/- mice, it was further confirmed that Sca-1high LMSCs promote tumorigenesis by recruiting macrophages, further supporting that the increased recruitment of macrophages mediates the pro-metastasis effect of Sca-1high LMSCs. Collectively, this study demonstrated that Sca-1high LMSCs and their effectors could be targeted to inhibit breast cancer metastasis to the lung."

Journal • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • CCL2 • CXCL1

CCL2 Inhibitor Bindarit Improve Postoperative Cognitive Function by Attenuating Pericyte Loss-Related Blood-Brain Barrier Disruption and Neuroinflammation. (PubMed, Mediators Inflamm) - "This study demonstrates that the CCL2 inhibitor Bindarit significantly reduces the incidence of PND by preventing PC loss, thereby protecting the BBB and alleviating neuroinflammation. These findings suggest that targeting CCL2 could be a potential therapeutic strategy for preventing and treating PND."

Journal • Anesthesia • CNS Disorders • Cognitive Disorders • Developmental Disorders • Inflammation • Musculoskeletal Diseases • Orthopedics • CCL2 • CLDN5 • GFAP • OCLN

A pH-responsive guanidino-based covalent organic framework nanodrugs for enhanced neuroprotection against subarachnoid hemorrhage by targeting NLRP3 inflammasome. (PubMed, Biomaterials) - "Bindarit, a β-blocker with anti-inflammatory properties, has demonstrated potential in mitigating NLRP3-mediated pyroptosis...The development of B@COFDT-R constitutes a substantial advancement in the treatment of SAH. Through the enhancement of drug delivery mechanisms and the targeted modulation of critical inflammatory pathways, this nanocarrier holds the potential to significantly improve therapeutic outcomes for patients suffering from SAH."

Journal • Cardiovascular • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • NLRP3

Engineering blood-brain barrier microphysiological systems to model Alzheimer's disease monocyte penetration and infiltration. (PubMed, Biomater Sci) - "Moreover, we also tested the interventions including Minocycline and Bindarit, and found they can effectively inhibit AD monocyte infiltration, subsequently reducing neuroinflammation and neuronal apoptosis. We believe these scalable and user-friendly BBB-MPS models may hold promising potential in modeling and advancing therapeutics for neurodegenerative and neuroinflammatory diseases."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Inflammation

Elucidating the therapeutic potential of indazole derivative bindarit against K-ras receptor: An in-silico analysis using molecular dynamics exploration. (PubMed, Biochem Biophys Rep) - "Consequently, further downstream signalling of the K-Ras pathway would be blocked and this could lead to the inhibition of K-Ras dependent cancer cell proliferation. However, further validation of present study can be done through experimental assay such as cytotoxic and protein expression analysis."

Journal • Colon Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Bindarit attenuates neuroinflammation after subarachnoid hemorrhage by regulating the CCL2/CCR2/NF-κB pathway. (PubMed, Brain Res Bull) - "Endogenous CCL2 expression was upregulated in the rat SAH model. Bindarit improved neurological functions and reduced neuroinflammation by regulating the CCL2/CCR2/NF-κB pathway in early brain injury after SAH."

Journal • CNS Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • Vascular Neurology • CCL2 • CCR2

Circulating monocyte adhesion repairs endothelium-denuded injury through downstream of kinase 3-mediated endothelialization. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "However, this process was inhibited by the CCR2B inhibitor INCB3344...Bindarit, a selective MCP1 inhibitor, suppressed endothelialization following CCAED surgery in WT mice but not in DOK3-/- mice. In conclusion, endothelialization mediated by circulating monocytes repairs endothelium-denuded injury to compensate for endothelial functions through MCP1/DOK3/CCR2B/Ca2+ signaling. Our findings indicate that circulating monocyte adhesion is an important endothelial wound healing mechanism."

Journal • Cardiovascular • Hematological Disorders • Thrombosis • CCL2 • CCR2

Impact of Bindarit, a CCL2 Chemokine Synthesis Inhibitor, on Macrophage-Based Biofouling and Continuous Glucose Monitoring in vivo. (PubMed, Biosens Bioelectron ) - "These results not only confirm the major role monocytes/macrophages play, but directly demonstrate that CCL2 drives Mo/MQ recruitment and biofouling of glucose sensors in vivo. These findings support future studies incorporating Mo/MQ migration/chemotaxis inhibitors, like CCL2, on sensor coatings to improve glucose sensor accuracy and lifespan in vivo."

Journal • Preclinical • Diabetes • Fibrosis • Immunology • Inflammation • Metabolic Disorders • CCL2 • CCR2

Unraveling morphine tolerance: CCL2 induces spinal cord apoptosis via inhibition of Nrf2 signaling pathway and PGC-1α-mediated mitochondrial biogenesis. (PubMed, Brain Behav Immun) - "Our data emphasize that chemokine CCL2 inhibited the Nrf2 signaling pathway and PGC-1α-mediated mitochondrial biogenesis, alleviating the occurrence of apoptosis in spinal cord, thereby participating in morphine tolerance. This may provide new targets for the treatment of morphine tolerance."

Journal • Inflammation • Neuralgia • Pain • CCL2

Exploring and Validating the Mechanism of Ulinastatin in the Treatment of Sepsis-Associated Encephalopathy Based on Transcriptome Sequencing. (PubMed, J Inflamm Res) - "A total of 106 hub - gene - related drugs were predicted, among which BINDARIT - CCL2 and LIFITEGRAST - ICAM1 showed particularly high affinities. In conclusion, ICAM-1, IRF7, IL-1β, CCL2, IL-6, and SOCS3 were identified as potential therapeutic targets in SAE mice treated with UTI. This study offers theoretical support for UTI as a treatment option for SAE."

Journal • CNS Disorders • Infectious Disease • Septic Shock • CCL2 • ICAM1 • IL1B • IL6 • IRF7 • SOCS3

Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus. (PubMed, Acta Pharm Sin B) - "Furthermore, the administration of CCR2 antagonist (INCB 3284) reduces ChP macrophage accumulation and ventriculomegaly. This study not only unveils the ChP CCL2‒CCR2 signaling in the pathophysiology of hydrocephalus but also unveils Bindarit as a promising therapeutic choice for the management of posthemorrhagic hydrocephalus."

Journal • CNS Disorders • Hematological Disorders • Inflammation • Ventriculomegaly • CCL2 • CCR2 • TNFA • TNFRSF1A

CCL2 promotes EGFR-TKIs resistance in non-small cell lung cancer via the AKT-EMT pathway. (PubMed, Acta Biochim Biophys Sin (Shanghai)) - "Conversely, CCL2 suppression by CCL2 synthesis inhibitor, bindarit, or CCL2 knockdown can reverse this resistance...In summary, CCL2 promotes the development of acquired EGFR-TKIs resistance and EMT while activating AKT signaling in NSCLC. These insights suggest a promising avenue for the development of CCL2-targeted therapies that prevent EGFR-TKIs resistance in NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCL2

Bindarit treatment results in minor effects in the FKRP-P448Lneo- mutant mouse (New Directions 2024) - No abstract available

Preclinical • Fibrosis • Immunology • Inflammation

CCL2-CCR2 AXIS MEDIATES DECIDUAL MONOCYTE/MACROPHAGE INFILTRATION AND INFLAMMATION IN OBSTETRIC ANTIPHOSPHOLIPID SYNDROME (EULAR 2024) - "The monocyte/macrophage infiltration and inflammation of blocking CCL2-CCR2 signaling in OAPS mice was investigated by bindarit, a CCL2 inhibitor, and RS504393, a CCR2 antagonist... The CCL2-CCR2 axis mediates monocyte/macrophage infiltration from peripheral blood to decidua, and subsequent inflammation, among OAPS. We provide a new insight into the mechanism and therapeutic target for OAPS."

Genetic Disorders • Hematological Disorders • Inflammation • Obstetrics • CCL2 • CCR2 • IFNG • TNFA

Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy. (PubMed, J Transl Med) - "Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • CCL2 • CCL8 • MRC1