paquinimod (ABR-215757) / Active Biotech - LARVOL DELTA

S100A8/A9 SIGNALING CAUSES MITOCHONDRIAL DYSFUNCTION AND MEGAKARYOCYTE APOPTOSIS IN ACUTE MYELOID LEUKEMIA (EHA 2025) - "S100a8/a9 signalling mediated mitochondrial dysfunction and MK apoptosis in the inflammatory microenvironment of AML leads to thrombocytopenia. Paquinimod may be used in combination with chemotherapy to enhance platelet count in AML by restoring MK apoptosis and improving mitochondrial function."

Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Metabolic Disorders • Oncology • Respiratory Diseases • Thrombocytopenia • CD34 • NRF1 • S100A8 • S100A9 • TLR4

Long Noncoding RNA Interleukin 6 Antisense RNA 1 Promotes Inflammatory Effects in Lung Macrophages via Exosomes Through the S100A9/TLR4 Pathway in Chronic Obstructive Pulmonary Disease Progression. (PubMed, MedComm (2020)) - "These findings suggest that IL6-AS1 may facilitate crosstalk between fibroblasts and macrophages, contributing to increased pulmonary inflammation, an effect that can be blocked by paquinimod. Mendelian randomization analysis further suggests a potential shared causal variant between IL6-AS1 and COPD risk. Taken together, this investigation provides valuable insights into the function of IL6-AS1 and its potential implications for the pathogenesis and therapeutic strategies in COPD."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL6 • S100A9 • TLR4

S100a8 inhibitor Paquinimod attenuates coal dust-induced pulmonary fibrosis via blocking neutrophils-S100a8-Tlr4-macrophages signaling axis. (PubMed, Int Immunopharmacol) - "In conclusion, our study elucidates the critical role of S100a8 in coal dust-induced pulmonary fibrosis and highlights the potential of S100a8 inhibition by Paquinimod as a therapeutic strategy. These findings provide insight into potential treatments for pulmonary complications associated with coal pneumoconiosis."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • FN1 • S100A8 • TGFB1 • TLR4 • TNFA

Macrophage-derived S100A9 promotes diabetic cardiomyopathy by disturbing mitochondrial quality control via STAT3 activation. (PubMed, Int J Biol Sci) - "S100A9 blocking by paquinimod or macrophage depletion (clodronate) alleviated diabetes-induced cardiac dysfunction, inflammatory macrophage infiltration, serum pro-inflammatory cytokines. Nevertheless, these effects were mitigated by STAT3(Y705F) mutation, STAT3 knockdown, or paquinimod. Our study highlights macrophage-derived S100A9 as a critical mediator for impaired mitochondrial quality control in diabetic cardiac dysfunction, and targeting S100A9 represents a promising therapeutic target."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Inflammation • Metabolic Disorders • CCR2 • S100A9 • STAT3

Calprotectin inhibition attenuates silica-induced lung fibrosis. (PubMed, Inflammopharmacology) - "This study aimed to investigate the role of calprotectin (S100A8/S100A9) as a pro-inflammatory and pro-fibrotic mediator in silica-induced lung fibrosis and evaluated the therapeutic potential of the calprotectin inhibitor, paquinimod...These findings highlighted calprotectin's pivotal role in silica-induced lung fibrosis and inflammation, suggesting that its inhibition could be a promising therapeutic approach for silicosis and other fibro-inflammatory lung diseases. Further research is warranted to explore the precise mechanisms linking calprotectin to lung fibrosis and its potential as a biomarker and therapeutic target."

Journal • Asthma • Cystic Fibrosis • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • COL1A1 • S100A8 • S100A9 • TLR4

S100A9 as a potential novel target for experimental autoimmune cystitis and interstitial cystitis/bladder pain syndrome. (PubMed, Biomark Res) - "S100A9 is an important pro-inflammatory and pathogenic molecule in IC/BPS and EAC. Targeting S100A9-initiated signalling pathways may offer a novel therapeutic strategy for IC/BPS."

Journal • CNS Disorders • Immunology • Inflammation • Interstitial Cystitis • Musculoskeletal Pain • Pain • S100A9 • TLR4

Identification of S100A9 as a target for diagnosis and treatment of Crohn's Disease after Vedolizumab treatment failure. (PubMed, Immunol Lett) - "Through flow cytometry, changes in the composition of immune cell populations in colon tissues were found after intragastric administration of paquinimod, an inhibitor of S100A9. It is important that blocking S100A9 inhibited the recruitment of neutrophils in the mice's colon. Our findings lay a foundation for the further exploration of the new targets for non-responders to vedolizumab in CD patients."

Journal • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • S100A9

Targeting Calprotectin S100A8/A9 to Overcome AML Progression in DNMT3A-Mutant Cells. (PubMed, Curr Med Sci) - "Elevated S100A8/A9 expression contributes to the abnormal proliferation, migration, adhesion, and chemoresistance of DNMT3Amut AML cells. Targeting S100A8/A9 alone or in combination with other treatments represents a promising therapeutic strategy for DNMT3Amut AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ANXA5 • CCL2 • DNMT3A • ICAM1 • MMP2 • S100A8 • S100A9 • VCAM1

Fibroblast Growth Factor 20 Attenuates Colitis by Restoring Impaired Intestinal Epithelial Barrier Integrity and Modulating Macrophage Polarization via S100A9 in an NF-κB Dependent Manner. (PubMed, Cell Mol Gastroenterol Hepatol) - "These results suggest that FGF20 acts as a negative regulator of S100A9 and NF-κB, thereby inhibiting M1 macrophage polarization and restoring intestinal epithelial barrier integrity in mice with DSS-induced colitis. FGF20 may serve as a potential therapeutic target for the treatment of ulcerative colitis."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis • S100A9

S100A8 induces Cyclophosphamide-Induced Alopecia via NCF2/NOX2-Mediated Ferroptosis. (PubMed, Free Radic Biol Med) - "Administration of the S100A8 inhibitor paquinimod (PAQ) alleviated alopecia and decreased markers of oxidative stress and ferroptosis. In vitro experiments using human outer root sheath keratinocytes (ORSKs) confirmed that S100A8 promotes ferroptosis via the NCF2/NOX2 pathway, as inhibition of NCF2 or NOX2 reversed these effects. These findings suggest that targeting the S100A8-NCF2/NOX2 axis may provide a novel therapeutic strategy for mitigating CIA induced by various chemotherapeutic agents."

Journal • Alopecia • Immunology • Inflammation • GPX4 • S100A8

Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury. (PubMed, Redox Biol) - "Finally, we established that the suppression of NET formation by S100A8/A9 inhibition is primarily mediated through the AMPK/Nrf2/HO-1 signaling pathway. These findings underscore the critical pathological role of S100A8/A9 in TBI and emphasize the need for further exploration of S100A8/A9 inhibitor Paquinimod as a potential therapeutic strategy for TBI."

Journal • CNS Disorders • Inflammation • Vascular Neurology • S100A8

S100A8/A9 Promotes Dendritic Cell-Mediated Th17 Cell Response in Sjögren's Dry Eye Disease by Regulating the Acod1/STAT3 Pathway. (PubMed, Invest Ophthalmol Vis Sci) - "Tear secretion, corneal fluorescein staining, and hematoxylin and eosin staining were used to evaluate the effect of paquinimod, a S100A8/A9 inhibitor, on dry eye disease in nonobese diabetic (NOD) mice...S100A8/A9 activated the Acod1/STAT3 pathway to promote DC-driven Th17 cell responses in SjDED. The S100A8/A9/Acod1/STAT3 pathway may represent a promising therapeutic target for SjDED."

Journal • Dry Eye Disease • Obesity • Ocular Inflammation • Ophthalmology • IL23A • S100A8

Mechanism of S100A9-mediated astrocyte activation via TLR4/NF-κB in Parkinson's disease. (PubMed, Int Immunopharmacol) - "C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 15 mg/kg four times daily) and subsequently treated with Paquinimod, a S100A9 inhibitor (7 mg/kg, once daily for 7 days, totaling 8 doses)...In vitro, TLR4/NF-κB inhibitors mitigated inflammation and A1/A2 polarization of astrocytic MA cells induced by recombinant S100A9 (rS100A9). These findings suggest that S100A9 mediates astrocyte neuroinflammation and A1/A2 polarization via TLR4/NF-κB signaling, highlighting its potential as a therapeutic target for PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • GFAP • IL1B • IL6 • PTX3 • S100A10 • S100A9 • TLR4 • TNFA

Single-cell RNA sequencing reveals S100A8/A9hi neutrophils-induced endothelial cell death and lymphocyte infiltration after ischemic stroke. (PubMed, Biochem Biophys Res Commun) - "Notably, the S100A8/A9 inhibitor paquinimod significantly protects neurons and reduces lymphocyte infiltration, suggesting that targeting S100A8/A9 could be a promising therapeutic strategy for reducing neurological deficits after ischemic stroke. Overall, these results enhance our understanding of the complex interactions between immune cells and the BBB in ischemic stroke, paving the way for innovative therapeutic approaches aimed at maintaining brain integrity and improving patient outcomes."

Journal • Cardiovascular • Inflammation • Ischemic stroke • CXCR2 • CXCR4 • S100A8

Retinal microglia-derived S100A9 incite NLRP3 inflammasome in a Western diet fed Ossabaw pig retina. (PubMed, bioRxiv) - "Inhibition of TLR4 with TAK242 and NLRP3 with MCC950 attenuated the production of IL-1β during S100A9 stimulus. Finally, pre-treatment with Paquinimod successfully reduced S100A9-driven increases of glycosylated-TLR4, NLRP3, ASC, Caspase-1, and IL-1β production. We demonstrated that microglial-derived S100A9 perpetuates pro-inflammatory responses via the NLRP3 inflammasome in the retina of young Western-diet-fed Ossabaw pigs exhibiting diabetic retinopathy."

Journal • Diabetes • Diabetic Retinopathy • Inflammation • Obesity • Retinal Disorders • Type 2 Diabetes Mellitus • CASP1 • CXCL8 • IL1B • IL6 • NLRP3 • S100A9 • TLR4

Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity. (PubMed, Front Immunol) - "Surprisingly, we found that blocking the extracellular TLR4 signaling from S100A9 using the inhibitor Paquinimod, resulted in increased tumor growth and a detrimental effect on anti-PD-L1 efficacy in the CT26 tumor model...Intratumoral injection of recombinant S100A9 early after mice inoculation with CT26 cells had an anti-tumor effect. These findings indicate an important yet understudied role of S100A9 as an alarmin and immune stimulatory signal in cancer settings, and highlight the potential to exploit such signals to promote beneficial anti-tumor responses."

IO biomarker • Journal • Infectious Disease • Oncology • S100A9

Paquinimod attenuates retinal injuries by suppressing the S100A9/TLR4 signaling in an experimental model of diabetic retinopathy. (PubMed, Exp Eye Res) - "Our study validates the S100A9/TLR4 pathway in diabetic retinas and suggests its potential as a therapeutic target for DR. Targeting S100A9 could offer a novel approach to prevention and treatment."

IO biomarker • Journal • Diabetes • Diabetic Retinopathy • Inflammation • Metabolic Disorders • Oncology • Retinal Disorders • S100A9

The role of the S100A8/S100A9 in gastric tumor progression. (PubMed, Sci Rep) - "In vitro experiments verified that S100A9 can promote the proliferation and migration of AGS cells through the TLR4-NFκB signaling pathway, and the S100A8/S100A9 inhibitor Paquinimod can inhibit their proliferation and migration...Macrophages with high expression of S100A8/S100A9 are critical in the progression of gastric inflammation to cancer. Cytokine S100A9 can activate the TLR4-NFκB signaling pathway and promote the proliferation and migration of gastric adenocarcinoma cells."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • S100A8 • S100A9 • TLR4

S100A9 promotes renal calcium oxalate stone formation via activating the TLR4-p38/MAPK-LCN2 signaling pathway. (PubMed, Int J Biol Macromol) - "S100A9 promotes renal inflammatory injury by activating the TLR4-p38/MAPK-LCN2 pathway and then contributes to CaOx stone formation."

Journal • Inflammation • Metabolic Disorders • Nephrology • CD68 • CD80 • KIM1 • LCN2 • S100A9 • TLR4

Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma. (PubMed, Inflamm Res) - "These findings highlight calprotectin as a potential therapeutic target regulated by IL-17 in steroid hyporesponsive asthma. Targeting calprotectin may offer a promising approach to alleviate airway inflammation and restore steroid responsiveness in severe asthma. Further investigations are warranted to explore its therapeutic potential in clinical settings and elucidate its broader implications in steroid mechanisms of action."

Journal • Asthma • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • IL17A • S100A8 • S100A9

S100A9-TLR4 axis aggravates dry eye through the blockage of autophagy. (PubMed, Exp Eye Res) - "Autophagic blockage was predicted by the scRNA-seq data in DED, and further verified by decrease of LC3B-II/LC3B-I and increase of SQSTM1 and p-mTOR/mTOR, while S100A9 inhibitor paquinimod (PAQ) reversed the changes...Finally, signs of DED, chronic corneal inflammation and cell death got a remission after either inhibition of S100A9 or TLR4. In general, we deduced a S100A9-TLR4-Autophagic blockage pathway in the pathogenesis of DED."

Journal • Dry Eye Disease • Inflammation • Keratitis • Ocular Inflammation • Ophthalmology • S100A9 • SQSTM1 • TLR4

S100A9 as a Key Myocardial Injury Factor Interacting with ATP5 Exacerbates Mitochondrial Dysfunction and Oxidative Stress in Sepsis-Induced Cardiomyopathy. (PubMed, J Inflamm Res) - "Targeted S100A9 inhibition by paquinimod partially reversed myocardial mitochondrial dysfunction and oxidative stress. The interaction of S100A9 with ATP5 exacerbates myocardial damage in sepsis by inducing mitochondrial dysfunction and oxidative stress."

Journal • Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Metabolic Disorders • Septic Shock • CASP4 • LRG1 • NLRP3 • OSMR • S100A8 • S100A9 • SERPINA3 • SOCS3 • TFAM

Neutrophil Adhesion-related S100A8/A9 and Neutrophil Extracellular Traps Production: A Vicious Cycle in Antiphospholipid Syndrome Thrombosis (ISTH 2024) - "The use of the S100A8/A9 inhibitor, paquinimod, effectively reduced NETs and thrombosis in animal models... We observed enhanced release of NETs and neutrophil adhesion in APS patients compared to healthy subjects, which may be related to endothelial damage. Additionally, scRNAseq results showed an increase in the expression of S100A8 and S100A9 in neutrophils from APS patients. Furthermore, the S100A8/A9 exhibited significant upregulation in APS patients and APS models."

Cardiovascular • Genetic Disorders • Hematological Disorders • Immunology • Thrombosis • S100A8 • S100A9

THE TRADITIONAL CHINESE MEDICINE QILIAN-XIAOPI COMPOUND AMELIORATE GASTRIC MUCOSAL DYSPLASIA THROUGH THE S100A9/TLR4/NFκB SIGNALING PATHWAY (DDW 2024) - "Our data indicates that the traditional Chinese medicine QLXP can function similarly to the S100A9 inhibitor Paquinimod. Its mechanism likely involves modulating proliferation and apoptosis through the S100A9/TLR4/NFκB signaling pathway thereby alleviating gastric mucosal dysplasia."

IO biomarker • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • S100A9 • TLR4

Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models. (PubMed, Brain Commun) - "Adjunctive therapy that improved clinical outcomes in multiple studies was dexamethasone (6 studies), C5 antibodies (3 studies) and daptomycin (3 studies). HMGB1 inhibitors, matrix metalloproteinase inhibitors, neurotrophins, antioxidants and paquinimod also improved clinical parameters but only in single or small studies...In conclusion, 24 of 54 treatment regimens (44%) tested improved clinically relevant outcomes in experimental pneumococcal meningitis but few were tested in multiple well-designed studies. The most promising new adjunctive treatments are with C5 antibodies or daptomycin, suggesting that these drugs could be tested in clinical trials."

Journal • Preclinical • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Infectious Disease • Inflammation • Otorhinolaryngology • Pneumococcal Infections • Pneumonia • Psychiatry • Vascular Neurology • HMGB1