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

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

Paquinimod-hydrogel hybrid microneedle array patch alleviates hypertrophic scar via inhibiting M1 polarization. (PubMed, Bioeng Transl Med) - "With the advantages of excellent penetrability, surface sealing, sustained release, and precise uniform distribution, PHMAP exhibited superior therapeutic efficacy over intravenous and intradermal injections. These results suggest that PHMAP can be a promising and advanced solution for HS prevention and therapies."

Journal • S100A8

Knockdown of S100A9 inhibits pyroptosis and promotes PPAR signaling pathway in atopic dermatitis. (PubMed, Biochem Biophys Res Commun) - "S100A9 knockdown inhibits pyroptosis and stimulates the PPAR signaling pathway in AD, which offers a potential strategy for AD treatment."

Journal • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IFNG • KRT16 • NLRP3 • PPARA • PPARG • S100A9 • SERPINB4 • TNFA

S100A9 inhibition ameliorates HFpEF by modulating mitochondrial fission and oxidative stress. (PubMed, Int Immunopharmacol) - "Inhibition of S100A9 with Paquinimod (PAQ) improved diastolic function, reduced cardiac hypertrophy, and decreased S100A9-positive macrophage infiltration, while preventing M1 macrophage polarization...Cardiomyocyte-specific PDK4 knockdown in vivo further ameliorated HFpEF progression without affecting systolic function. These findings highlight S100A9 inhibition as a promising therapeutic strategy for HFpEF by targeting mitochondrial dysfunction through the S100A9/SPI1/PDK4 axis."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • PDK4 • S100A9 • SPI1

S100a9 Aggravates Ischemia Brain Injury via Pyroptosis Pathway: A Potential Prognostic Biomarker and Therapeutic Target for Ischemic Stroke. (PubMed, J Neurochem) - "Pharmacological targeting of S100a9 using Paquinimod and siRNA-mediated knockdown further defined its functional regulation of pyroptotic cascades. Results demonstrate that S100a9 amplifies neuroinflammatory responses and microglia-specific pyroptosis, correlating with worsened infarct volumes and poor 30-day modified Rankin Scale scores. Targeted S100a9 inhibition attenuated brain injury and neuroinflammation, highlighting its potential as a therapeutic target for stroke intervention."

Biomarker • Journal • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology • S100A9

Mechanism of Neutrophil p90RSK-Nrf2 Signaling Pathway in Atherosclerosis. (PubMed, Balkan Med J) - "Paquinimod, an MRP8/14 antagonist, mitigated neutrophil activation, inflammation, and arterial plaque formation. MRP8/14 secreted from neutrophils activates the ERK1/2-p90RSK pathway via TLR4 and suppresses the NRF2-ARE pathway, driving inflammation and promoting AS progression."

IO biomarker • Journal • Atherosclerosis • Cardiovascular • Inflammation • ITGAM

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