BAY86-5047 / Bayer - LARVOL DELTA

Effect and mechanism of chemokine receptor 1 in airway inflammation in a mouse model of chronic obstructive pulmonary disease. (PubMed, Exp Lung Res) - "The COPD model mice exhibited significantly increased expression levels of p-IKK, p-JAK2, STAT3, and p-p65 and chemokine concentrations (MIP-1β, IL-6 and TNF-α) than the control mice (p < 0.05), which were further aggravated by overexpressed-CCR1 lentiviral transfection but inhibited by shRNA-CCR1 lentiviral transfection or BX471 pretreatment (p < 0.05). CCR1 aggravates the progression of COPD mice by activating JAK/STAT3/NF-κB signaling. This study has the potential to provide theoretical evidence for the diagnosis and therapeutic strategies of cigarette smoke-induced inflammation in COPD patients."

Journal • Preclinical • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL4 • CCR1 • IL6 • JAK2 • TNFA

Tumor-derived CCL5 recruits CCR1+ macrophages to suppress apoptosis and drive proliferation in duodenal adenocarcinoma. (PubMed, Cancer Lett) - "Functional assays demonstrated that CCL5 promoted CCR1+ macrophage migration, an effect suppressed by both the CCR1 antagonist BX471 and CCL5-neutralizing antibody...Together, our findings establish the CCL5/CCR1 axis as a key mediator of tumor-macrophage crosstalk in DA, supporting immune evasion and chemoresistance via suppression of macrophage-induced apoptosis. Targeting this axis may represent a promising therapeutic strategy to enhance the efficacy of conventional chemotherapy in DA."

Journal • Gastrointestinal Cancer • Oncology • Small Intestinal Carcinoma • CCL5

Stress Promotes Lung Metastasis in Breast Cancer by Altering Neutrophil Differentiation. (PubMed, Cancer Res) - "Targeting this axis using an anti-Ly6G antibody to deplete neutrophils, a CRISPR/Cas9-mediated approach to conditionally knockout Ccl3/Ccl4 in neutrophils, and BX471 treatment to inhibit CCR1 in cancer cells all significantly reduced breast cancer lung metastasis. Together, this study not only demonstrates a stress-neutrophil-cancer axis that promotes lung metastasis in breast cancer but also provides potential strategies for reducing lung metastasis by targeting CSP neutrophils or CCR1+ breast cancer cells."

Journal • Breast Cancer • Oncology • Solid Tumor • Transplantation • CCL3 • CCL4 • CEBPB • IL1R2

The Mechanism of Immunotherapeutic Resistance in Pulmonary Sarcomatoid Carcinoma (IASLC-WCLC 2025) - "Experimental mice were divided into four groups, with the exposure of following drugs: IPG1576 (MIF inhibitor; 10 mg/kg, i.p., q2d), BX471 (CCR1 antagonist; 50 mg/kg, s.c., q2d), Camrelizumab, Ociperlimab and Maraviroc [CCR5 antagonist] (all 10 mg/kg, i.p., q3d). In humanized PDX models (Fig.1M), the CCR1/CCR5 inhibitor combination (G4) outperformed MIF inhibitor/ anti-TIGIT (G3) (Figs.1O-P), reversing resistance by increasing precursor-exhausted and reducing terminal-exhausted CD8+ T cells (Fig.1Q). These findings identify CCR1/CCR5 blockade as a novel strategy to reverse immunotherapeutic resistance in PSC Conclusions : The additional combination of CCR1/CCR5 blockade with anti-PD-1 demonstrated a synergistic efficacy to immunotherapy-resistant tumors via reshaping the microenvironment, potentially offering a novel approach to combat immunotherapy resistance in PSC."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • CCL3 • CD8 • CXCL10 • CXCL5 • GZMK • LDHB • NECTIN2 • SLC8A1 • TIGIT

Investigating the Role of the Chemokine Receptor, CCR1 in Cutaneous Lupus Erythematosus Pathogenesis (FOCIS 2025) - "We plan to test the CCR1 antagonist BX471 in our mouse model, as it blocks both T cells and monocytes, potentially offering better protection against disease. The CCR1 chemokine axis plays a major role in recruiting disease-causing immune cells to the skin. Blocking this axis with antagonists may help protect against the development of CLE in our mouse model."

Cutaneous Lupus Erythematosus • Immunology • Inflammation • Inflammatory Arthritis • Lupus • CCL23 • CCL3 • CCL8 • CCR1

The Chemokine (C-C Motif) Receptor 1 Antagonist BX471 Improves Fluid Resuscitation in Rat Models of Hemorrhagic Shock. (PubMed, Biomedicines) - "BX471-treatment reduced TNFα and IL6 concentrations in large intestine extracts (p < 0.05). Our findings suggest CCR1 as a new therapeutic target to reduce fluid requirements during resuscitation from hemorrhagic shock."

Journal • Preclinical • Hematological Disorders • Inflammation • CCL3 • CCR2 • CCR3 • IL6 • MPO • TNFA

NOVEL FINDINGS ON CCR1 RECEPTOR IN CNS DISORDERS: A PATHOGENIC MARKER USEFUL IN CONTROLLING NEUROIMMUNE AND NEUROINFLAMMATORY MECHANISMS IN PARKINSON'S DISEASE (ADPD 2025) - " In this study, we probed the neuroprotective properties of the CCR1 antagonist BX471 compound in a mouse model of MPTP -induced nigrostriatal degeneration... In light of these findings, CCR1 could represent a useful pathological marker of PD, and its targeting could be a worthy candidate for the future development of new immunotherapies against PD."

IO biomarker • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

CCR1 inhibition sensitizes multiple myeloma cells to glucocorticoid therapy. (PubMed, Pharmacol Res) - "We show that blocking CCR1 signaling with the antagonist BX471 enhances the anti-MM effects of the glucocorticoid dexamethasone in MM cell lines, primary patient material and a myeloma xenograft mouse model. Our findings suggest that CCR1 may play a role in glucocorticoid resistance, as the GC-induced downregulation of CCR1 mRNA and protein is blunted in a GC-resistance onset model. Moreover, we demonstrate that inhibiting CCR1 partially reverses this resistance, providing a promising strategy for resensitizing MM cells to GC treatment."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CCL3

Blocking the CCL5/CCL7-CCR1 axis regulates macrophage polarization through NF-κB pathway to alleviate the progression of osteoarthritis. (PubMed, Int Immunopharmacol) - "CCL5/CCL7-CCR1 axis was involved in macrophage polarization, and blocking it could reduce synovitis and alleviate the process of OA."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • CCL7 • NFKBIA

CCR1 Antagonist as a Potential Modulator of Inflammatory, Autophagic, and Apoptotic Markers in Spinal Cord Injury. (PubMed, Neuropharmacology) - "The highest efficacy was observed at the 10 mg/kg dose, leading to optimal out-comes across the assessments. These findings suggest that CCR1 blockade with BX471 may offer a promising therapeutic strategy for SCI, addressing a critical gap in the current pharmacological treatment options."

Journal • CNS Disorders • Inflammation • Orthopedics • IL1B • TNFA

Gram-negative microflora discrepancy facilitates tumor progression and immune evasion by activating CCL3/CCL5-CCR1-MAPK-PD-L1 pathway in esophageal squamous cell carcinoma (AATS-ITSOS 2024) - "Human ESCC cells KYSE150 and TE1 were co-cultivated with Jurkat cells with different lipopolysaccharide (LPS) or BX471 concentrations to examine the effect of G- bacterial flora on the occurrence of ESCC and immune escape... Our results revealed that Gram-negative microflora dysbacteriosis can induce immune evasion in ESCC. LPS accumulation in ESCC microenvironment upregulated CCL3/CCL5 -CCR1-MAPK-PD-L1 pathway and promoted both tumor malignant biological behavior and T cell exhaustions."

Gram negative • IO biomarker • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Infectious Disease • Oncology • Solid Tumor • Squamous Cell Carcinoma • CCL3 • CCR1 • LAG3 • LAMP1 • PD-1

Inhibition of CC chemokine receptor 1 ameliorates osteoarthritis in mouse by activating PPAR-γ. (PubMed, Mol Med) - "This study demonstrated the expression of CCR1 in chondrocytes. Inhibiting CCR1 reduced the inflammatory response, alleviated cartilage aging, and retarded degeneration through the MAPK signaling pathway and PPAR-γ, suggesting its potential therapeutic value for OA."

Journal • Preclinical • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • ACAN • CCR1 • CDKN1A • CDKN2A • IL1B • MMP13 • PPARA • PTGS2 • SOX9

Biased Signaling of Chemokine Receptor CCR1 in Asthma (ATS 2024) - "BX471 is the most widely used CCR1 antagonist in basic studies... CCR1 mediates eosinophil differentiation via β-arrestin-biased signaling, which plays a critical role in asthmatic inflammation. Inhibiting the function of β-arrestin is a pivotal step in the development of small molecule inhibitors targeting CCR1."

Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Novel Findings on CCR1 Receptor in CNS Disorders: A Pathogenic Marker Useful in Controlling Neuroimmune and Neuroinflammatory Mechanisms in Parkinson's Disease. (PubMed, Int J Mol Sci) - "In this study, we probed the neuroprotective properties of the CCR1 antagonist BX471 compound in a mouse model of MPTP-induced nigrostriatal degeneration...In addition, biochemical analyses carried out on serum revealed a considerable increase in circulating levels of CCR1 following MPTP-induced PD. In light of these findings, CCR1 could represent a useful pathological marker of PD, and its targeting could be a worthy candidate for the future development of new immunotherapies against PD."

Biomarker • IO biomarker • Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling. (PubMed, J Agric Food Chem) - "The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling."

Journal • Acute Lung Injury • Respiratory Diseases • CD68 • IL10 • IL18 • IL1B • IL4 • IL6 • MRC1 • NAMPT • NLRP3 • TLR2 • TNFA

The interplay of Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils proactively mediates silica-induced pulmonary fibrosis. (PubMed, J Hazard Mater) - "In vivo, administration of clodronate liposomes, Cxcl10 or Mmp14 siRNA-loaded liposomes, Ccl3 receptor antagonist BX471, CD44 or CSF1R neutralizing antibodies significantly alleviated silica-induced lung fibrosis. Collectively, these results demonstrate that the newly defined Cxcl10+/Mmp14+ monocytes and Ccl3+ neutrophils participate in the silicosis process and highlight anti-receptor-ligand pair treatment as a potentially effective therapeutic strategy in managing silicosis."

Journal • Fibrosis • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL3 • CSF1R • CXCL10 • HBEGF • MMP14

Network pharmacology combines machine learning, molecular simulation dynamics and experimental validation to explore the mechanism of acetylbinankadsurin a in the treatment of liver fibrosis. (PubMed, J Ethnopharmacol) - "Our results suggest that ACBA significantly attenuated CCl4-induced liver fibrosis in histopathological and serum liver function analyses. This effect may be mediated by CCR1, NF-κB and STAT1 signalling."

Journal • Machine learning • Fibrosis • Gastrointestinal Disorder • Hepatology • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammatory Arthritis • Liver Cirrhosis • Oncology • Rheumatoid Arthritis • Rheumatology • AKR1B1 • CCR1 • CDK1 • CYP3A4 • EPHA3 • IL17A • IL6 • NFKBIA • PFKFB3 • TNFA

Chemokine receptor CCR1 regulates macrophage activation through mTORC1 signaling in nonalcoholic steatohepatitis. (PubMed, Metabolism) - "Ccr1 deficiency mitigated macrophage activity by inhibiting mTORC1 signaling, thereby preventing the development of NASH. Notably, the CCR1 inhibitor BX471 protected against NASH. These findings would help in developing novel strategies for the treatment of NASH."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Biased signaling of chemokine receptor CCR1 in asthma (ERS 2023) - "Intriguingly, we found that BX471 selectively inhibited G protein, rather than β-arrestin signaling of CCR1, which might contribute to its failure in clinic trials. Thus, our studies identified the key function of CCR1 biased signaling in asthma pathogenesis, as well as providing the basis for the design of CCR1-targeted biased antagonists for asthma treatment.; Endoscopy and interventional pulmonology; Imaging; Cell and molecular biology"

Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Chemokine Receptor CCR1: A New Target for Asthma Treatment (ERS 2023) - "By using single-particle cryo-electron microscopy, we recently solved the structures of CCR1 in complex with CCL15 and its antagonist BX471. Together with functional results, our studies revealed the structural basis of ligand recognition and receptor activation of CCR1, as well as provided multiple templates for rational design of therapeutics targeting CC chemokine receptors.; Endoscopy and interventional pulmonology; Imaging; Cell and molecular biology"

Asthma • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL23

Blockade of CCR1 induces a phenotypic shift in macrophages and triggers a favorable antilymphoma activity. (PubMed, Blood Adv) - "Therapeutic in-vivo targeting of CCR1 with CCR1 antagonist BX471 significantly reduced FC-muMCL-1 mouse tumors in the syngeneic MCL model by depletion of M2-TAMs and by increased infiltration of cytotoxic CD8+ T cells. Our study established that CCR1 exerts a pivotal role in macrophage programming, thus shaping protumor TME and lymphoma progression. CCR1 inhibition through CCR1 antagonists may be a promising therapeutic strategy to reprogram macrophages in lymphoma-TME and achieve better clinical outcomes in patients."

Journal • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCL3 • CCR1 • CD8 • IL10 • MRC1 • STAT1 • TNFA

Effects of blocking chemokine receptor CCR1 with BX471 in two models of fibrosis prevention and rescue in mice. (PubMed, Biochem Biophys Rep) - "Our data indicate that BX471 treatment did neither affect serum and tissue markers of liver injury and fibrosis in the CCl model and only moderately in the Abcb4 model of biliary fibrosis. The animal models indicate that treatment with BX471 alone is unlikely to exert major beneficial effects in chronic liver disease."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • ABCB4

Chemokine receptor antagonists with α-adrenergic receptor blocker activity. (PubMed, J Basic Clin Physiol Pharmacol) - "Our data suggest that CCR antagonists should be screened for cross-reactivity with α-adrenoceptors to exclude potential adverse cardiovascular effects when used as anti inflammatory drugs."

Journal • Cardiovascular • CCR10 • CCR4

Eosinophil-derived chemokine (hCCL15/23, mCCL6) interacts with CCR1 to promote eosinophilic airway inflammation. (PubMed, Signal Transduct Target Ther) - "Eosinophil differentiation and airway inflammation were remarkably decreased by the specific CCR1 antagonist BX471. Thus, the study identifies that the CCL6-CCR1 axis is involved in the crosstalk between eosinophils and HSCs during the development of allergic airway inflammation, which also reveals a potential therapeutic strategy for targeting G protein-coupled receptors (GPCRs) for future clinical treatment of asthma."

Journal • Asthma • Eosinophilia • Immunology • Inflammation • Respiratory Diseases • CCL23

Therapeutic Effect of C-C Chemokine Receptor Type 1 (CCR1) Antagonist BX471 on Allergic Rhinitis. (PubMed, J Inflamm Res) - "In addition, BX-471 exhibits anti-allergic effect by increasing Treg cell population. Overall, BX471 represents a promising therapeutic strategy against AR."

IO Biomarker • Journal • Allergic Rhinitis • Immunology • CCL5 • CSF2 • NFKB1 • TLR4 • TNFA • VCAM1