- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Calprotectin is regulated by IL-17A and induces steroid hyporesponsiveness in asthma. (Pubmed Central) - Nov 6, 2024
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.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal, PD(L)-1 Biomarker, IO biomarker: Blocking S100A9-signaling is detrimental to the initiation of anti-tumor immunity. (Pubmed Central) - Nov 5, 2024
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.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: S100A9-TLR4 axis aggravates dry eye through the blockage of autophagy. (Pubmed Central) - Sep 12, 2024
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.
- |||||||||| paquinimod (ABR-215757) / Active Biotech, Cubicin (daptomycin) / Merck (MSD)
Preclinical, Review, Journal: Adjunctive treatments for pneumococcal meningitis: a systematic review of experimental animal models. (Pubmed Central) - May 6, 2024
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.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Targeting S100A9 Prevents ?-Adrenergic Activation-Induced Cardiac Injury. (Pubmed Central) - Mar 6, 2024
In the current study, initially, we validated the role of S100A8/A9 in contributing to cardiac injury and heart failure via the overactivation of the ?-adrenergic pathway and tested the potential use of paquinimod as a pharmacological intervention of S100A8/A9 activation in preventing cardiac dysfunction, collagen deposition, inflammation, and immune cell infiltration in ?-adrenergic overactivation-mediated heart failure...Our results revealed that targeting S100A9 provides dual beneficial effects, which is not only a strategy to counteract cardiac inflammation but also preclude cardiac fibroblast-macrophage interactions. The findings of this study also indicate that targeting S100A9 could be a promising strategy for addressing cardiac fibrosis, potentially leading to future drug development.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease. (Pubmed Central) - Sep 11, 2023
Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin...These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Preclinical, Journal, IO biomarker: Blockage of S100A8/A9 ameliorates septic nephropathy in mice. (Pubmed Central) - Aug 7, 2023
Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD. In this research, Septic AKI was triggered by cecal ligation and puncture (CLP) operation in wild-type mice, which treated with or without an S100A9 inhibitor, Paquinimod (Paq, 10
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Single-cell transcriptome profiling of sepsis identifies HLA-DRS100A monocytes with immunosuppressive function. (Pubmed Central) - Jun 20, 2023
In this research, Septic AKI was triggered by cecal ligation and puncture (CLP) operation in wild-type mice, which treated with or without an S100A9 inhibitor, Paquinimod (Paq, 10 This study identifies HLA-DRS100A monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal, Immune cell: Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging. (Pubmed Central) - Jun 7, 2023
Notably, treatment with S100A8 inhibitor paquinimod rejuvenates BAT axon networks and thermogenic function in aged male mice. Our study suggests that targeting the bone marrow-derived senescent immune cells presents an avenue to improve BAT aging and related metabolic disorders.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Targeting S100A9 Signaling Reduces Lung Cell Death and Inflammation in Alpha-1 Antitrypsin Deficiency (Walter E. Washington Convention Center, Area D, Hall C (Lower Level)) - Mar 25, 2023 - Abstract #ATS2023ATS_8524;
Here, we hypothesize that targeting S100A9 signaling could alter inflammation and cell fate in AAT-deficient animals and HBE cells.Methods used: Male and female age-matched Serpina1a-e knockout mice were orally administered the S100A9 inhibitor, paquinimod, daily for 4 months...AAT also reduced S100A9-induced apoptosis determined by Annexin V staining using flow cytometry.Conclusions of the study: In conclusion, inhibition of S100A9 reduced AAT deficiency-associated inflammation and lung cell death. Therefore, S100A9 signaling plays a major role in several mechanisms associated with AAT deficiency emphysema.
- |||||||||| dorsomorphin (Compound C) / EMD Serono, paquinimod (ABR-215757) / Active Biotech
Journal: Deficiency of S100A9 Alleviates Sepsis-Induced Acute Liver Injury through Regulating AKT-AMPK-Dependent Mitochondrial Energy Metabolism. (Pubmed Central) - Feb 12, 2023
Finally, the administration of the S100A9 inhibitor Paquinimod (Paq) to WT mice protected against CLP-induced mortality, liver injury and mitochondrial dysfunction. In summary, our findings demonstrate for the first time that S100A9 plays an important pro-inflammatory role in sepsis-mediated ALI by regulating AKT-AMPK-dependent mitochondrial energy metabolism and highlights that targeting S100A9 may be a promising new approach for the prevention and treatment of sepsis-related liver injury.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: S100a8/a9 contributes to sepsis-induced cardiomyopathy by activating ERK1/2-Drp1-mediated mitochondrial fission and respiratory dysfunction. (Pubmed Central) - Jan 20, 2023
Here, septic cardiomyopathy was induced with cecal ligation and puncture (CLP) in S100a9-knockout (KO) mice lacking the heterodimer S100a8/a9 or wild-type (WT) mice administered with an S100a9-specific inhibitor Paquinimod (Paq), which prevents the binding of S100a9 toTLR4...Finally, administration of Paq to WT mice markedly prevented the CLP-induced cardiomyopathy mitochondrial fission and dysfunction compared with vehicle control. In summary, our data reveal, for the first time, that S100a8/a9 plays a critical role in mediating SIC, presumably by activating TLR4-ERK1/2-Drp1-dependent mitochondrial fission and dysfunction and highlight that blockage of S100a8/a9 may be a promising therapeutic strategy to prevent SIC in patients with sepsis.
- |||||||||| Iclusig (ponatinib) / Takeda, Otsuka, Incyte
Journal, IO biomarker: Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. (Pubmed Central) - Jan 11, 2023
Taken together, these findings uncover a novel mechanism of ponatinib-induced cardiac inflammation leading to cardiac dysfunction. From a translational perspective, our results provide critical preclinical data and rationale for a clinical investigation into immunosuppressive interventions for managing ponatinib-induced cardiotoxicity.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal, IO biomarker: Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. (Pubmed Central) - Aug 17, 2022
Pyroptotic platelet-derived oxidized mitochondrial DNA (ox-mtDNA) potentially promoted neutrophil extracellular trap (NET) formation, which contributed to platelet pyroptosis by releasing S100A8/A9, forming a positive feedback loop that led to the excessive release of inflammatory cytokines. Both pharmacological inhibition using Paquinimod and genetic ablation of the S100A8/A9-TLR4 signaling axis improved survival in mice with CLP-induced sepsis by suppressing platelet pyroptosis.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Targeting S100A9 Signaling Protects Lung Function in Alpha-1 Antitrypsin Deficiency (Area F, Hall F (North Building, Exhibition Level), Moscone Center) - Feb 19, 2022 - Abstract #ATS2022ATS_4911;
Targeting S100A9 signaling countered loss of lung function in Serpina1a-e knockout mice. Therefore, S100A9 signaling plays a major role in the lung disease associated with AAT deficiency.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Preclinical, Journal: Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund's Adjuvant. (Pubmed Central) - Jan 18, 2022
Concomitantly, p20 activated caspase-1, IL-1β, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1β.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Preclinical, Journal: Role of the Alarmin S100A9 protein in inducing Achilles tendinopathy in rats. (Pubmed Central) - Jan 7, 2022
In this study, 40 male Sprague-Dawley rats were randomly divided into four groups: Control group (received no treatment), Injury group (Achilles tendon tissues were cut intraoperatively), S100A9 group (received a subcutaneous injection of rhS100A9 solution), and S100A9 + Paquinimod group [received a subcutaneous injection of rhS100A9 and Paquinimod (1:1 ratio) into the Achilles tendon]...Additionally, a large number of tendon cells had died in both the Injury and S100A9 groups. This study showed that Alarmin S100A9 can induce AT-like morphological changes and local inflammatory reactions, trigger collagen fiber remodeling and tendon cell apoptosis, and ultimately induce AT.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Preclinical, Journal: S100A9 Upregulation Contributes to Learning and Memory Impairments by Promoting Microglia M1 Polarization in Sepsis Survivor Mice. (Pubmed Central) - Oct 9, 2021
Thus, we used S100A9 inhibitor Paquinimod to study the role of S100A9 in cognitive impairments in CLP-induced and LPS-induced mice models of SAE...Notably, S100A9 inhibition significantly improved the survival rate and learning and memory impairments in sepsis survivors, with a shift from M1 to M2 phenotype. Taken together, our study suggests that S100A9 upregulation might contribute to learning and memory impairments by promoting microglia M1 polarization in sepsis survivors, whereas S100A9 inhibition might provide a potential therapeutic target for SAE.
- |||||||||| ketamine / Generic mfg.
Journal: Progress in the development of kynurenine and quinoline-3-carboxamide derived drugs. (Pubmed Central) - Mar 5, 2021
4-Cl-KYN has completed clinical trials in depression without success...Quinoline-3-carboxamide derivatives laquinimod, paquinimod, and tasquinimod show structural similarities to kynurenines...Further clarification may emerge from studies involving higher drug concentration, and/or from identification of ketamine targets. Clinical application trials in very diverse indications of structurally related quinoline-3-carboxamides and the wide range of their mode of action warrant further studies permitting direct comparison of effects and better target identification.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19. (Pubmed Central) - Mar 4, 2021
A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 was dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain anti-viral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
- |||||||||| paquinimod (ABR-215757) / Active Biotech
Journal: Platelet-neutrophil interaction aggravates vascular inflammation and promotes the progression of atherosclerosis by activating the TLR4/NF-κB pathway. (Pubmed Central) - Jul 9, 2020
Normal diet or high-fat diet ApoE mice with or without administration of Mrp8/14 antagonist paquinimod were used for plasma collection to measure total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, TNF-α, IL-1β, Mrp8/14, TLR4, and nuclear factor (NF)-κB p65 levels...Conversely, Mrp8/14/TLR4/NF-κB interference alleviated AS progression. In conclusion, Mrp8/14/TLR4/NF-κB activated by platelet-neutrophil interaction is an important inflammatory signaling pathway for AS pathogenesis.
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