PMX 53 / Teva - LARVOL DELTA

Spatial compartmentalization of complement signaling dichotomously controls macrophage fate and immunopathology in tuberculosis (ERS 2026) - "Mechanisms were dissected in human macrophages using the Mtb virulence factor ESAT-6, employing compartment-specific C5aR1 antagonists (cell-permeable JPE1375 vs. impermeable PMX53) and mitochondrial functional assays... We define a "Complement Geography" paradigm in TB: infection outcome depends on the balance between protective extracellular C1q and destructive intracellular mtC5aR1 signaling. Targeting the intracellular CFB-C5a-mtC5aR1 axis offers a precise therapeutic strategy to block pathological pyroptosis."

Infectious Disease • Respiratory Diseases • Tuberculosis • NLRP3 • PTX3

Palmitic Acid Amplifies Microglial Inflammatory Activation Involving C5aR1-Sensitive Inflammatory Signaling and JMJD3/H3K27me3-Related Epigenetic Changes. (PubMed, J Neuroimmune Pharmacol) - "Under heat-inactivated serum conditions, PA increased cell-associated C5a immunoreactivity and extracellular C5a levels, and these C5a-related readouts were reduced by PMX53...Pharmacological KDM6 inhibition with GSK-J4 attenuated PA-associated increases in IL-1β and IL-6 expression. Together, these findings support the involvement of C5aR1-sensitive inflammatory signaling and JMJD3/H3K27me3-related epigenetic regulation in PA-associated microglial inflammatory responses."

Journal • CNS Disorders • Inflammation • CD86 • FOS • IL1B • IL6 • JUN • KDM6B • MRC1 • TLR4 • TNFA

Minimally invasive extracorporeal circulation protects against postoperative pulmonary endothelial injury in elderly cardiac surgery via suppressing the C5a-mtDNA-cGAS-STING axis: a mechanistic randomized controlled trial. (PubMed, Int Immunopharmacol) - "MiECC is a safe, effective perfusion strategy that mitigates postoperative pulmonary exudation in elderly cardiac surgical recipients. At the mechanistic level, MiECC restricts CPB-induced C5a overproduction, thereby preventing C5a-driven mitochondrial impairment and mtDNA release, which initiates the cGAS-STING inflammatory cascade. Selective C5aR blockade fully interrupts this pathological axis, providing robust translational evidence to support broader adoption of MiECC in high-risk elderly patients and identifying C5aR as a tractable therapeutic target for CPB-associated lung injury."

Journal • Cardiovascular • Inflammation • Metabolic Disorders • Respiratory Diseases • STING

C5a/C5aR1 mediates AKI-CKD transition by enhancing autophagy. (PubMed, Nephrol Dial Transplant) - "Our data reveal a detrimental role of the C5a/C5aR1 axis in AKI-to-CKD transition by triggering macrophage polarization towards a chronic inflammatory phenotype and disrupting mitochondrial homeostasis via the involvement of BNIP3-regulated autophagy in kidney tubular epithelial cells, leading to tubulointerstitial fibrosis and kidney dysfunction. Targeting C5aR1 may provide a promising therapeutic strategy for preventing CKD progression."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Nephrology • Renal Disease • Reperfusion Injury • TNFA

Complement C5a Promotes Epithelial-Mesenchymal Transition in Pterygium via C5aR Activation. (PubMed, Invest Ophthalmol Vis Sci) - "Functional validation was conducted using primary conjunctival epithelial cells (PCECs) treated with C5a with or without the C5aR antagonist PMX53...Notably, C5a also increased VEGFA expression. These findings suggest that C5a/C5aR signaling may contribute to pterygium pathogenesis by promoting EMT-related changes in conjunctival epithelial cells, supporting C5aR as a potential therapeutic target."

Journal • Ophthalmology • CDH1 • VIM

Inhibition of C5aR1 alleviates early brain injury after subarachnoid hemorrhage by reducing STAT3 phosphorylation and attenuating neuroinflammation. (PubMed, Brain Res Bull) - "PMX53 and STAT3-IN-13 inhibit JAK/STAT3-p65 phosphorylation, reduce TNF-α/IL-1β, and increase TGF-β/IL-10. C5a promotes STAT3 phosphorylation through C5aR1, thereby exacerbating neuroinflammation, making C5aR1 a potential therapeutic target."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Subarachnoid Hemorrhage • Vascular Neurology • C5AR1 • IL10 • IL1B • TGFB1 • TNFA

Activation of the C3a-C3aReceptor-axis is associated with endothelial dysfunction and glycocalyx damage in ST-elevation myocardial infarction. (PubMed, Basic Res Cardiol) - "C3a-receptor-antagonists (SB290157 and JR14a), C5a-Receptor1-antagonism (PMX53), as well as Rac1-Inhibition (NSC23766) were used to verify pathway specificity and downstream signaling involvement. C3a:C3a-Receptor signaling drives Rac1-mediated cytoskeletal stiffening, eGC degradation, NO reduction, and leukocyte adhesion, promoting endothelial dysfunction in STEMI in both macrovascular and microvascular endothelial cells. This pathway represents a potential therapeutic target to mitigate complement-mediated vascular injury in acute myocardial infarction."

Journal • Cardiovascular • Myocardial Infarction • Reperfusion Injury • SDC1

The Intracellular C5a-mtC5aR1 Axis Promotes Necroptosis in Dry Eye Through DRP1-Mediated Mitochondrial Dysfunction. (PubMed, Invest Ophthalmol Vis Sci) - "The functional role of the intracellular C5a-mtC5aR1 axis was assessed through pharmacological inhibition (JPE-1375 and PMX-53) and analysis of downstream signaling (RIPK3/MLKL-mediated necroptosis, DRP1 activation, mitochondrial function, and inflammatory cytokine production)...Our findings identify the intracellular C5a-mtC5aR1-DRP1 axis as a novel regulatory mechanism driving necroptosis in DE. Targeting this pathway represents a potential therapeutic approach to reduce inflammation and corneal damage in DE."

Journal • Corneal Abrasion • Dry Eye Disease • Inflammation • Metabolic Disorders • Ocular Inflammation • Ophthalmology • C5AR1

Chronic stress promotes pancreatic ductal adenocarcinoma progression via complement C5a-recruited myeloid-derived suppressor cells. (PubMed, Cancer Immunol Immunother) - "The effect was abrogated by the C5aR1 antagonist PMX-53, identifying C5a as a critical mediator of MDSC accumulation. Intervention with the ADRB1 antagonist atenolol in PDAC mice significantly reduced serum/tumoral C5a levels, diminished splenic/intratumoral MDSCs proportions, and attenuated tumor growth. Our findings propose that targeting the SNS-driven complement-MDSCs axis represents a promising strategy for PDAC patients."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • PD-L1 • TGFB1

Research progress on the complement system in ischemia-reperfusion injury of organ transplantation. (PubMed, Transplant Rev (Orlando)) - "Advances in therapeutic research highlight the values of complement inhibitors, including anti-C5 agents (e.g., eculizumab) that mitigate delayed graft function (DGF) in kidney transplantation, C1 esterase inhibitors that attenuate IRI and antibody-mediated rejection (AMR), C5a receptor antagonists (e.g., PMX53) that extend graft survival in preclinical models, and soluble complement receptor 1 (sCR1) that alleviates multi-organ IRI. Future research should focus on optimizing organ-specific targeting strategies, validating the long-term efficacy and safety of these agents via clinical trials, and exploring synergistic immunomodulatory approaches to further improve transplantation outcomes."

Journal • Review • Antibody-mediated Rejection • Cardiovascular • Hepatology • Inflammation • Liver Failure • Reperfusion Injury • Solid Organ Transplantation • Transplantation

Glioblastoma-derived ribosomal protein S19 exacerbates cerebral edema through C5AR1 in tumor-associated macrophages (SNO 2025) - "The RPS19-C5AR1 axis drives GBM-associated cerebral edema by promoting IL-1β-mediated astrocyte reprogramming and inflammatory signaling. Targeting this pathway with agents such as PMX-53 may mitigate edema and its protumoral consequences in GBM."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • AQP4 • C5AR1 • CCL2 • CD68 • IL1B • IL6 • SPI1 • TGFB1

Glioblastoma-derived ribosomal protein S19 exacerbates cerebral edema through C5AR1 in tumor-associated macrophages (WFNOS 2025) - "The RPS19-C5AR1 axis drives GBM-associated cerebral edema by promoting IL-1β-mediated astrocyte reprogramming and inflammatory signaling. Targeting this pathway with agents such as PMX-53 may mitigate edema and its protumoral consequences in GBM."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor • AQP4 • C5AR1 • CCL2 • CD68 • IL1B • IL6 • SPI1 • TGFB1

tRF3a-MetCAT Promotes EGFR-Targeted Therapeutic Resistance through the TRIM21-STAT1-C5a Axis in Lung Adenocarcinoma. (PubMed, Research (Wash D C)) - "In vivo, treatment with the C5a-targeting inhibitor eculizumab or the C5a receptor inhibitor PMX53 effectively mitigates tRF3a-MetCAT-induced osimertinib resistance. These results reveal novel resistance pathways in EGFR-mutant lung cancer and suggest therapeutic approaches to addressing EGFR-TKI resistance."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • STAT1 • TRIM21

Bmpr2 Drives Aberrant Activation and Injury of Glomerular Endothelial Cells in Lupus Nephritis. (PubMed, J Am Soc Nephrol) - "These findings highlight BMPR2 as a key regulator of glomerular endothelial cell injury and macrophage-mediated inflammation in lupus nephritis. Targeting BMPR2 or its upstream activators, such as C5a, effectively treated and improved lupus nephritis."

Journal • Glomerulonephritis • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus • CD86 • ICAM1 • VCAM1

Prenatal betamethasone-postnatal N-methyl-D-aspartic acid model of spasms: Update on mechanisms and treatments. (PubMed, Epilepsia Open) - "FDA-approved therapies/medications, ACTH and vigabatrin, have limited efficacy and significant side effects, necessitating further research into better therapies...The C5a receptor antagonist PMX53 shows efficacy in males, suggesting inflammation may be a therapeutic target...Some therapies, like AQB-565, show promise in reducing seizures with fewer side effects. Our findings suggest that personalized, targeted treatments based on individual causes and sex differences could improve outcomes."

Journal • Cardiovascular • CNS Disorders • Developmental Disorders • Epilepsy • Inflammation

ACSL4 Drives C5a/C5aR1-Calcium-Induced Fibroblast-to-Myofibroblast Transition in a Bleomycin-Induced Mouse Model of Pulmonary Fibrosis. (PubMed, Biomolecules) - "Pharmacological inhibition of ACSL4 (PRGL493) or C5aR1 (PMX53) attenuated the deposition of ECM and suppressed the expression of fibrotic markers in vivo and in vitro. These findings demonstrate that ACSL4 functions downstream of C5a/C5aR1-induced calcium signaling to promote FMT and the progression of pulmonary fibrosis. Targeting ACSL4 may therefore offer a novel therapeutic strategy for IPF."

Journal • Preclinical • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • ACSL4

C5a/C5aR1 upregulates thyroid cell glycolysis and promotes epithelial-mesenchymal transition in Hashimoto's thyroiditis (ATA 2025) - "In animal experiments, CBA/J mice were divided into control (n = 10), experimental autoimmune thyroiditis (EAT) (n = 10) and EAT+C5aR1 antagonist (PMX53) (n = 10) groups... EMT occurs in HT thyrocytes. In HT, abnormal increased C5a may enhance the LDHA-mediated glycolysis in thyrocytes and induce EMT, thus promoting thyroid fibrosis. C5aR1 antagonist can partially inhibit EMT in thyrocytes."

Late-breaking abstract • Endocrine Disorders • Fibrosis • Immunology • C5AR1 • LDHA • TG

PTX3 Deficiency Aggravates Periodontitis by the Complement C5a-C5aR1 Axis. (PubMed, J Dent Res) - "Inhibition of C5a signaling with PMX53 or NLRP3 inflammasome with MCC950 significantly alleviated these adverse effects...In vitro studies showed that PTX3 deficiency promoted C5a conversion and release in monocytes, thereby activating the NLRP3 inflammasome via the C5a-C5aR1 axis-mediated mitogen-activated protein kinase and nuclear factor κB signaling in an inflammatory environment. In conclusion, these data elucidate the link between PTX3 in regulating complement activation and periodontitis progression, providing a potential target for innate immune-based therapy of periodontitis."

Journal • Dental Disorders • Inflammation • Osteoporosis • Periodontitis • NLRP3 • PTX3

Autoantibodies cause nociceptive sensitization in a mouse model of degenerative osteoarthritis. (PubMed, Pain) - "Monosodium iodoacetate-injected joints demonstrate elevated levels of complement component 5a (C5a) and C5a receptor blockade using intra-articular PMX-53-reduced sensitization. These data suggest that MIA-treated mice and patients with OA generate pronociceptive antibodies, and further support the pronociceptive autoimmunity hypothesis for the transition from tissue injury to chronic musculoskeletal pain."

Journal • Preclinical • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

The activation of complement C5a-C5aR1 axis in astrocytes facilitates the neuropathogenesis due to EV-A71 infection by upregulating CXCL1. (PubMed, J Virol) - "Notably, EV-A71 infection led to activation of the C5a-C5aR1 axis in U87-MG cells, and knockdown (siC5aR1) or blockade (PMX53) of C5aR1 significantly suppressed EV-A71-induced astrocyte activation and proinflammatory cytokine (e.g., CXCL1) production...In addition, neutralizing CXCL1 significantly alleviates the neuropathogenesis caused by EV-A71 infection. Thus, inhibiting the C5a-C5aR1 axis has emerged as a potential therapeutic strategy to mitigate neural damage caused by EV-A71 infection."

Journal • CNS Disorders • Infectious Disease • Inflammation • CXCL1 • IL6

Dysregulated complement activation during acute myocardial infarction leads to endothelial glycocalyx degradation and endothelial dysfunction via the C5a:C5a-Receptor1 axis. (PubMed, Front Immunol) - "Endothelial cells were stimulated with C5a or patient sera (with/without C5a-receptor1 antagonist "PMX53") and the nanomechanical properties of eGC quantified using the atomic force microscopy (AFM)-based nanoindentation technique...This study demonstrates that dysregulated C5a activation during AMI results in eGC damage with subsequent endothelial dysfunction and reduced NO bioavailability, indicating progressively developing vascular inflammation. This could be prevented by antagonizing C5aR1, highlighting the role of the C5a:C5a-Receptor1 axis in vascular inflammation development and endothelial dysfunction in AMI, offering new therapeutic approaches for future investigations."

Journal • Cardiovascular • Inflammation • Myocardial Infarction • RAC1 • RHOA

An herbal formula Shenlian decoction upregulates M1/M2 macrophage proportion in hepatocellular carcinoma by suppressing complement cascade. (PubMed, Biomed Pharmacother) - "The suggested mechanism was demonstrated by application of C5aR1 inhibitor, PMX-53 in mouse HCC model...SLD could suppress the C5 secretion in hepatoma cells via inhibition of AMPK/p38 signaling. We suggested that SLD is a potential herbal therapy for the treatment of HCC by alleviating immune-suppressive status."

Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • C5AR1 • CTNNB1 • MET

Blockade of C5aR1 resets M1 via gut microbiota-mediated PFKM stabilization in a TLR5-dependent manner. (PubMed, Cell Death Dis) - "Therefore, in this study, genetic deletion of C5ar1 or pharmacological inhibition of C5aR1 with anti-C5aR1 Ab or PMX-53 in the presence or absence of deletion Abs were utilized to verify if and how C5aR1 inhibition regulated TAMs polarization via affecting gut microbiota composition...Our data revealed that high levels of C5aR1 in TAMs predicted poor prognosis. In summary, our study suggested that C5aR1 inhibition reduced CRC growth via resetting M1 by AKT2 activation-mediated PFKM stabilization in a TLR5-dependent manner, which relied on IL-22-regulated gut flora."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AKT2 • IL22 • PFKM • TLR5

Polystyrene microplastics induce kidney injury via gut barrier dysfunction and C5a/C5aR pathway activation. (PubMed, Environ Pollut) - "Further experiments using a C5aR inhibitor, PMX53, verified the vital role of renal C5a/C5aR pathway activation in the development of kidney injury induced by PS-MPs. Collectively, our results suggest that PS-MPs induce kidney injury in mice by impairing the gut barrier, increasing C5a levels, and ultimately activating the renal C5a/C5aR pathway, highlighting the crucial role of the gut-kidney axis in PS-MPs-induced kidney injury."

Journal • Chronic Kidney Disease • Gastrointestinal Disorder • Nephrology • Renal Disease

C5aR1 blockade reshapes immunosuppressive tumor microenvironment and synergizes with immune checkpoint blockade therapy in high-grade serous ovarian cancer. (PubMed, Oncoimmunology) - "Transcriptomic analyses of the xenografts delineated the mechanisms driving the immunomodulatory activity of PMX53, an orally bioavailable C5aR1 inhibitor...Furthermore, the combination of C5aR1 and PD-L1 was associated with specific molecular characteristics and matched clinical response annotations. Therefore, the abundance of C5aR1 could predict an inferior prognosis in HGSCs, and incorporating PD-L1 may serve as a novel predictive biomarker to guide therapeutic options."

Biomarker • Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • Tumor microenvironment • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor