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

S100A8/A9 Inhibition Reduces Neutrophil Extracellular Trap Formation and Mitigates Sepsis-Related Liver Injury. (PubMed, J Inflamm Res) - "This study suggests that elevated S100A8/A9 and concurrent NETosis are closely associated with sepsis-related liver injury (SRLI). S100A8/A9 can be used as a potential predictive biomarker for early liver dysfunction, and prophylactic administration of paquinimod can reduce intrahepatic inflammation, reduce NET formation, and improve the survival rate of mice with sepsis."

Journal • Critical care • Hepatology • Infectious Disease • Liver Failure • Oncology • Septic Shock • IL6 • S100A8 • TNFA

Targeting S100A8 mitigates pathogenic neutrophil-driven tissue injury in bacterial epididymo-orchitis. (PubMed, Biochem Biophys Res Commun) - "Notably, pharmacological inhibition of the S100A8/S100A9 complex with paquinimod reduced this pathogenic neutrophil infiltration and preserved testicular architecture. Together, these findings identify S100A8 as a key marker and candidate contributor to neutrophil-mediated tissue injury, and suggest that this axis warrants further investigation as a targeted immunomodulatory strategy that may help preserve fertility during bacterial infections."

Journal • Infectious Disease • Infertility • Inflammation • Sexual Disorders • ITGAM • S100A8 • S100A9

S100A9 as a shared biomarker and mediator of metabolic dysfunction in peripheral artery disease and sarcopenia. (PubMed, Front Genet) - "DGIdb screening identified Paquinimod, a selective S100A9 inhibitor with Phase II clinical safety data, as a candidate for therapeutic repositioning. This study reveals that upregulation of skeletal muscle inflammation and abnormal branched-chain amino acid metabolism may be common features of PAD and sarcopenia. BCKDHB, PIM1, JAML, NFE2, and S100A9 were identified as common diagnostic biomarkers, and metabolomics further confirmed that S100A9 may be a potential intervention target."

Biomarker • Journal • Cardiovascular • Inflammation • Metabolic Disorders • Myositis • Peripheral Arterial Disease • Sarcopenia • PIM1 • S100A9

A multi-target nano-therapy against cerebral ischemia/reperfusion injury via combinatorial inhibition of neuroinflammation and pyroptosis. (PubMed, J Mater Chem B) - " we synthesized CX3CL1-functionalized ZIF-8 nanoparticles co-loaded with disulfiram (DFL, a GSDMD-N pore inhibitor), paquinimod (PAQ, a TLR4/NF-κB inhibitor), and siNINJ1 (inhibiting membrane rupture). In vivo and in vitro results demonstrated that they synergistically inhibited the TLR4/NF-κB/NLRP3 signaling axis and pyroptosis execution (GSDMD, caspase-1), promoted microglial polarization towards the M2 phenotype, reduced pro-inflammatory cytokines (IL-6, TNF-α), and alleviated oxidative stress and neuronal apoptosis, ultimately leading to significantly reduced infarct volume and improved neurological recovery. we successfully developed an "active targeting-multi-drug synergy-cascade intervention" nano-therapeutic platform that effectively mitigates cerebral I/R injury through multi-pathway coordination, offering a novel combinatory strategy for ischemic stroke treatment."

Journal • Cardiovascular • Inflammation • Ischemic stroke • Reperfusion Injury • CX3CL1 • IL6 • NLRP3 • TLR4 • TNFA

Targeting IL-17-Mediated Immune–Neural Crosstalk in Skin to Alleviate Diabetic Neuropathy (AANP 2026) - "Treatment of DN mice with the S100A8/A9 inhibitor paquinimod reduced skin inflammation and reversed DN... Our data suggest that DN pain and pathology may result from IL-17-associated skin inflammation and the subsequent sensitization of DRG neurons. Our findings highlight the potential of repurposing the FDA-approved IL-17-targeting therapeutics as a novel treatment for DN."

Dermatitis • Diabetic Neuropathy • Immunology • Inflammation • Pain • Psoriasis • IL17A • IL17RA • S100A8

Targeting S100A8/A9 Ameliorates Heart Failure with Preserved Ejection Fraction by Modulating TLR4/NF-κB-Mediated Inflammation. (PubMed, Clin Exp Pharmacol Physiol) - "Inhibition of S100A8/A9-mediated inflammation improved diastolic function and reversed the pathological changes of the heart in mice with HFpEF. The observed effects were potentially mediated via inhibition of the TLR4/NF-κB pathway. The present study identified S100A8/A9 as a possible therapeutic target in HFpEF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation • S100A8 • TLR4

S100A8/A9 blockade attenuates autoimmune neuroinflammation by regulating the heterogeneity and function of neutrophils. (PubMed, Brain Behav Immun) - "Furthermore, we found that paquinimod treatment decreases neutrophil accumulation, which is associated with suppressed neutrophil production. Our findings highlight the therapeutic potential of targeting S100A8/A9 to modulate neutrophil heterogeneity and mitigate autoimmune pathology in MS/EAE treatment."

Heterogeneity • Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • S100A8

Paquinimod Targeting of the S100A8/A9 Axis Suppresses Liver Metastasis in Aged Mice. (PubMed, Cancers (Basel)) - " These findings indicate that aging is associated with a distinct hepatic immune context that shapes the inflammatory and cellular composition of the tumor microenvironment during liver metastasis. S100A9 emerges as a key age-associated, host-derived factor that is functionally relevant to the growth of liver metastases in aged hosts, supporting the S100A8/A9 axis as a context-specific therapeutic target."

Journal • Preclinical • Oncology • CD8 • S100A8 • S100A9

Elucidating the therapeutic efficacy and mechanisms of arctigenin in ameliorating renal fibrosis: a combined transcriptomic and proteomic study. (PubMed, Front Pharmacol) - "Using paquinimod, a specific S100A8/A9 inhibitor, we further demonstrated that pharmacological blockade of this pathway recapitulated the anti-fibrotic effects of ATG, providing causal evidence for its functional relevance. ATG exhibits therapeutic effects in ameliorating RF. Its mechanism involves regulating the TCA cycle and oxidative phosphorylation impairments via the S100A8/A9/NOX/NF-κB signaling pathway, thereby inhibiting inflammation and oxidative stress-driven EMT to improve RF."

Journal • Fibrosis • Immunology • Inflammation • S100A8 • TGFB1

S100A8/A9 promotes renal fibrosis by driving macrophage-to-myofibroblast transition via the TLR4/NF-κB pathway. (PubMed, Int Immunopharmacol) - "Moreover, both in vitro and in vivo, knockdown of S100A9 or pharmacological inhibition with the S100A8/A9 inhibitor paquinimod blocked the activation of the toll-like receptor 4 (TLR4)/ myeloid differentiation primary response gene 88 (MyD88)/ nuclear factor kappa-B (NF-κB) signaling pathway, reduced M2 macrophage polarization, and attenuated MMT. These findings suggest that S100A8/A9 may drives M2 macrophage-mediated MMT via the TLR4/NF-κB pathway, thereby promoting renal fibrosis. Therefore, targeting S100A8/A9 may represent a promising approach for the treatment of renal fibrosis in CKD."

IO biomarker • Journal • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • CD68 • MYD88 • S100A8 • S100A9 • TGFB1

Inhibition of S100A9 Mitigates Aging-Related Mitochondrial Dysfunction and Neurodegeneration in Parkinson's Disease. (PubMed, Neurochem Int) - "C57BL/6J mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP; 15 mg/kg four times daily), followed by Paquinimod (a S100A9 inhibitor; 7 mg/kg, once a day for 7 days after model establishment, totaling 8 doses)...Studies have shown that S100A9 plays a key bridge between aging and neurodegeneration in PD. Inhibition of S100A9 may be a potential therapeutic strategy to alleviate cell senescence and mitochondrial damage in PD."

Journal • CNS Disorders • Metabolic Disorders • Movement Disorders • Parkinson's Disease • CDKN1A • IL1B • IL6 • LMNB1 • MMP9 • S100A9

Identification of the Hub genes and inhibitors associated with hypertension in children with obesity using WGCNA. (PubMed, Front Cardiovasc Med) - "Small molecule inhibitor ABR-215757 (Paquinimod) was identified as a promising candidate, enhancing tube formation in the human umbilical vein endothelial cells (HUVECs) and reducing inflammatory markers. Targeting S100A9 may restore endothelial function and offer novel therapeutic strategies for obesity-related hypertension in children. More future research should validate these findings through in vivo models and clinical trials to evaluate the efficacy and safety of S100A9 inhibitors in pediatric populations."

Journal • Cardiovascular • Genetic Disorders • Hypertension • Inflammation • Obesity • Pediatrics • S100A9

S100A8/A9 inhibition reduces splenic myelopoiesis and improves outcomes after stroke. (PubMed, Front Immunol) - "Treatment with ABR-215757 led to reduced splenic myelopoiesis, reversed neutrophilia, enhanced forelimb grip strength, and a one-third reduction in infarct size at 24 hours post-stroke. These findings identify the spleen as a key contributor to neutrophil production following stroke and suggest that targeting S100A8/A9 may mitigate myeloid skewing and improve neurological recovery."

Journal • Cardiovascular • Inflammation • S100A8

Comparative cross-species transcriptomics during RSV infection identifies targets to treat RSV disease. (PubMed, J Infect) - "Inhibiting these with the anti-inflammatory drug Paquinimod reduced disease. Here we demonstrate that integrating mouse and human transcriptomic data can identify novel targets to treat RSV disease."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IL17A • S100A8 • S100A9

Calprotectin Is a Circulating Biomarker and Potential Therapeutic Target for Sarcopenia in Chronic Obstructive Pulmonary Disease. (PubMed, J Cachexia Sarcopenia Muscle) - "Serum calprotectin levels can be used to accurately predict sarcopenia in patients with COPD, and the calprotectin inhibitor paquinimod is a potential treatment for CS-induced skeletal muscle dysfunction."

Biomarker • Journal • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • Sarcopenia • Targeted Protein Degradation

S100A8/A9hi macrophage activates intestinal fibroblast via mCCL6/hCCL15-CCR1 axis to drive intestinal fibrosis in Crohn’s disease (ECCO-IBD 2026) - "Paquinimod, an inhibitor of S100A8/A9, significantly ameliorated fibrosis in colitic mice. Conclusion Our findings revealed that targeting S100A8/A9 hi macrophage may be a therapeutic strategy against intestinal fibrosis in CD."

Crohn's disease • Immunology • Inflammatory Bowel Disease • S100A8 • S100A9 • STAT3

Tissue-specific dysregulation of S100A8 in synovium and cartilage reveals limitations of NSAID therapy in inflammatory arthritis. (PubMed, Int Immunopharmacol) - "Furthermore, pharmacological inhibition of S100A8 with Paquinimod-particularly when combined with diclofenac-significantly reduced paw swelling, attenuated synovial and cartilage damage, suppressed inflammasome and MMP activation, and promoted a robust shift from pro-inflammatory M1 to anti-inflammatory M2 macrophage polarization. These findings highlight the cooperative anti-inflammatory benefits of dual S100A8 inhibition and NSAID treatment, and further support S100A8 as a key mediator of persistent inflammation and a promising therapeutic target in inflammatory arthritis."

Journal • Immune Modulation • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • S100A8

Mechanism study on Smilax glabra flavonoids in improving cardiac aging in rats by inhibiting S100A8/A9-mediated activation of p38 MAPK/NF-κB pathway (PubMed, Zhongguo Zhong Yao Za Zhi) - "For the in vitro experiment, a cellular aging model was constructed by using D-gal-induced H9c2 cardiomyocytes, with the S100A8/A9 inhibitor paquinimod(PAQ) and S100A8/A9 overexpression plasmids employed to validate the underlying mechanisms...The effects of PAQ intervention were similar to those of SGF; however, these effects were reversed by S100A8/A9 overexpression. In conclusion, SGF may inhibit the activation of the S100A8/A9-mediated p38 MAPK/NF-κB inflammatory pathway to further mitigate oxidative stress, mitochondrial dysfunction, and inflammatory responses, thereby alleviating D-gal-induced cardiac aging in rats."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Oncology • CAT • CDKN1A • CDKN2A • IL6 • S100A8 • TNFA • TP53

S100A8/S100A9 through PAD4 activation of neutrophil extracellular traps promotes granulomatous lobular mastitis. (PubMed, Front Immunol) - "S100A8/S100A9 plays a critical role in promoting NET formation via PAD4 activation. Targeting this axis with paquinimod effectively inhibits NETosis and alleviates GLM, suggesting a promising therapeutic strategy for GLM and other inflammatory diseases."

Journal • Inflammation • MPO • S100A8 • S100A9

Paquinimod regulate megakaryocyte function by restoring mitochondrial oxidative phosphorylation in acute myeloid leukemia (ASH 2025) - "The combination of cytarabine chemotherapy andPaquinimod increased the proportion of MK in the bone marrow, increased the MKP and MEPpopulations, reduced the level of MK apoptosis in the bone marrow, improved the expression of genesrelated to oxidative phosphorylation, and increased the levels of platelets and hemoglobin.ConclusionsIn AML, the inflammatory molecules S100a8/a9 mediate mitochondrial dysfunction and MK apoptosisthrough the TLR4/ERK-NRF1 signaling pathway, thereby leading to thrombocytopenia. Paquinimod, whenused in combination with chemotherapy, improves the mitochondrial function of megakaryocytes toalleviate thrombocytopenia in AML patients."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Metabolic Disorders • Ovarian Cancer • Thrombocytopenia • BCL2 • CASP3 • NRF1 • S100A8 • S100A9 • TLR4

S100A8 and S100A9-mediated keratinocyte affecting T lymphocyte immune imbalance through TLR4/NF-κ B in psoriasis. (PubMed, Acta Histochem) - "In this study, we found that both S100A8 and S100A9 were highly expressed in cells treated with M5-a cytokine mixture containing IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α-as well as in a mouse model of imiquimod (IMQ)-induced psoriasis. In particular, when the S100A8 and S100A9 inhibitor paquinimod was added to a mouse model of imiquimot-induced psoriasis, psoriatic dermatitis and inflammatory factors were reduced, and the expression of TLR4/NF-κB was also significantly reduced. In conclusion, this study illustrated that S100A8 and S100A9 participates in the pathogenesis of psoriasis by activating TLR4/NF-κB signaling pathways, thereby promoting psoriasis-associated skin inflammation, which suggested the potential role of S100A8 and S100A9 in the development of psoriasis and provided new insight into targeted therapies."

IO biomarker • Journal • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • IL17A • IL22 • S100A8 • S100A9 • TLR4 • TNFA

Suppression of the neutrophil-derived S100A8/A9 complex ameliorates doxorubicin-induced cardiomyopathy in non-human primates. (PubMed, Biochem Pharmacol) - "After paquinimod (inhibitor of S100A8/A9) was administered to the monkeys together with DOX, cardiac function was preserved and cardiomyocyte damage was prevented. Taken together, the DOX-induced cardiomyopathy model was successfully generated in the cynomolgus monkey. The S100A8/A9 complex may play a causal role in the onset and exacerbation of DOX-induced cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Inflammation • Oncology • S100A8 • S100A9

S100A8/9-NLRP3-mediated chronic unresolved inflammation drives cardiac pathologies following invasive pneumococcal disease. (PubMed, Exp Mol Med) - "This inflammation was central to the cardiac pathology because interventions with broad-spectrum immunosuppressive hydrocortisone or specific inhibitors of S100A9 (paquinimod) essentially rescued the Spn-induced cardiac pathologies. These results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing Spn-mediated cardiac pathologies in convalescence."

Journal • Cardiovascular • Infectious Disease • Inflammation • Pneumococcal Infections • Pneumonia • Respiratory Diseases • NLRP3 • S100A8 • S100A9 • TLR4

Neural stem cell-delivered oncolytic virus via intracerebroventricular administration enhances glioblastoma therapy and immune modulation. (PubMed, J Immunother Cancer) - "NSCs serve as efficient OV carriers, enhancing tumor targeting, suppressing GBM progression, and modulating the immune landscape. The combination with Paquinimod amplifies therapeutic benefits, offering a promising strategy for improving GBM treatment outcomes."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Immune Modulation • Immunology • Infectious Disease • Oncology • Solid Tumor • S100A8

Euchrenone A10 attenuates septic lung injury though S100A8/A9-dependent TLR4/MyD88/NF-κB signaling. (PubMed, Phytomedicine) - "A10 exerts its anti-inflammatory effects by binding to the S100A8/A9 protein, thereby inhibiting the TLR4-NF-κB inflammatory cascade. These properties highlight its therapeutic potential as monotherapy for SALI."

Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Septic Shock • MYD88 • S100A8 • S100A9 • TLR4