PMX 53 / Teva - LARVOL DELTA

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

C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway. (PubMed, Cardiovasc Res) - "High level of C5a was associated with increased risk of VC, and it accelerated VC by activating the receptor C5aR1. PERK-eIF2α-ATF4-CREB3L1 pathway of endoplasmic reticulum stress was activated by C5a-C5aR1, hence promoting VSMCs osteogenic transdifferentiation. Targeting C5 or C5aR1 may be an appealing therapeutic target for VC."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • ATF4 • COL1A1 • CREB3L1

Blockade of C5aR1 alleviates liver inflammation and fibrosis in a mouse model of NASH by regulating TLR4 signaling and macrophage polarization. (PubMed, J Gastroenterol) - "Blockade of the C5a-C5aR1 axis reduces hepatic steatosis, inflammation, and fibrosis in NASH mice. Our data suggest that C5aR1 may be a potential target for drug development and therapeutic intervention of NASH."

IO biomarker • Journal • Preclinical • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • Oncology • Solid Tumor • IL1B • NF-κβ • NLRP3 • TGFB1 • TLR4 • TNFA

Valproic acid attenuates cellular senescence in diabetic kidney disease through the inhibition of complement C5a receptors. (PubMed, Sci Rep) - "Similar results were observed in diabetic mice treated with a C5aR1 inhibitor, PMX53...Collectively, these results for the first time demonstrated that complement C5a mediates cellular senescence in diabetic kidney disease. Cellular senescence has been implicated in the pathogenesis of diabetic kidney disease, thus therapies to inhibit cellular senescence such as complement inhibitors present as a novel therapeutic option to treat diabetic kidney disease."

Journal • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Metabolic Disorders • Nephrology • Renal Disease

Investigating the Dynamic Binding Behavior of PMX53 Cooperating with Allosteric Antagonist NDT9513727 to C5a Anaphylatoxin Chemotactic Receptor 1 through Gaussian Accelerated Molecular Dynamics and Free-Energy Perturbation Simulations. (PubMed, ACS Chem Neurosci) - "Therefore, pose 2 (ΔG = -16.27 kcal/mol) is notably stable than pose 1 (ΔG = -9.78 kcal/mol) in the ternary complex. The identification of a novel binding mode of PMX53 and the detailed structural information of PMX53 interacting with a receptor obtained by GaMD simulations will be helpful in designing potent antagonists of C5aR1."

Journal

Complement activation contributes to subretinal fibrosis through the induction of epithelial-to-mesenchymal transition (EMT) in retinal pigment epithelial cells. (PubMed, J Neuroinflammation) - "Complement activation is critically involved in the development of subretinal fibrosis, partially through C5a-C5aR-mediated EMT in RPE cells. Targeting complement activation rather than C5a may be a novel approach for the management of macular fibrosis."

Journal • Age-related Macular Degeneration • Fibrosis • Immunology • Inflammation • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration • CDH1 • FN1 • IL6 • SNAI2 • TGFB1 • VIM

High Throughput Screen Identifies Drugs That Rescue AMD Phenotype in iPSC Derived RPE Model of Macular Degeneration (ASGCT 2022) - "Receptor blockers Compstatin (C5aR1), PMX53 (C3aR1), and depleted sera for C5 and C3 were used to confirm the role of the complement pathway... C5a and C3a induced sub RPE deposits in iPSC-RPE were rescued by two drugs discovered from the high throughput screening. The AMD model helped us in dissecting out the cell autonomous role of RPE in disease pathogenesis. It also provides a platform to study the genotype-phenotype relation in AMD."

Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • APOE • ATG5 • EZR • RELA • VIM

Regulatory relationship between macrophage autophagy and PVL-positive methicillin-resistant Staphylococcus aureus. (PubMed, Immunobiology) - "The results showed that PVL-MRSA could induced the autophagy of macrophages, which in turn reduced the damage from macrophages, which were respectively alleviated by 3-MA and aggravated by rapamycin...Exogenous rPVL, particularly A-Luk S-PV, administrated into macrophages also caused the autophagy of macrophage, which was reversed by PMX53, a C5aR antagonist...In conclusion, this study indicated PVL-MRSA regulated macrophage autophagy, which in turns inhibit the phagocytosis of S. aureus by macrophage. This study may provide a potential target against S. aureus infection."

Journal • Infectious Disease • Pneumonia • Respiratory Diseases

Complement C5a induces the generation of neutrophil extracellular traps by inhibiting mitochondrial STAT3 to promote the development of arterial thrombosis. (PubMed, Thromb J) - "By inhibiting mitochondrial STAT3 to elicit Mito-ROS generation, C5a triggers the generation of NETs to promote the development of arterial thrombosis. Hence, our study identifies complement C5a as a potential new target for the treatment and prevention of thrombosis."

Journal • Cardiovascular • Hematological Disorders • Immunology • Inflammation • Myocardial Infarction • Thrombosis • STAT3

Effect of a C5a receptor antagonist on macrophage function in an intestinal transplant rat model. (PubMed, Transpl Immunol) - "Inhibition of C5a/C5aR1 signaling appears to regulate macrophage differentiation and suppress rejection in small intestine transplantation immunity."

Journal • Preclinical • Transplantation • IL1B • TNFA

In Vivo Pharmacodynamic Method to Assess Complement C5a Receptor Antagonist Efficacy. (PubMed, ACS Pharmacol Transl Sci) - "Pharmacokinetic analysis demonstrated rapid plasma distribution and elimination of both compounds, although PMX53 had a longer half-life, which allowed for the development of an accurate pharmacokinetic/pharmacodynamic model. Overall, our study developed a robust in vivo pharmacodynamic model for C5aR1 inhibitors in mice that may assist in preclinical translational studies of therapeutic drug candidates targeting C5a and its receptors."

Journal • PK/PD data • Preclinical • Immunology • Inflammation