Tyrisa (darapladib) / GSK - LARVOL DELTA

Comparative effectiveness of anti-inflammatory therapies for atherosclerotic cardiovascular disease: a systematic review and network meta-analysis of 16 randomised trials (ESC 2026) - "Canakinumab 150 mg and colchicine both significantly reduce MACE in patients with atherosclerotic cardiovascular disease, though colchicine's benefit appears driven by MI prevention rather than mortality reduction. Darapladib and methotrexate are ineffective. The MACE benefit of colchicine persists even after incorporating the neutral CLEAR SYNERGY trial, but the absence of any mortality signal and low confidence of evidence for hard endpoints warrant cautious interpretation and continued investigation."

HEOR • Retrospective data • Review • Atherosclerosis • Cardiovascular • Myocardial Infarction

PLA2G7-Mediated Pro-Inflammatory Activation of Lipid-Associated Macrophages Drives Pulpitis. (PubMed, Int Endod J) - "These findings identify PLA2G7 as a potential biomarker for pulpitis and reveal a JUND-PLA2G7-LPC signalling axis linking lipid metabolism to macrophage-mediated inflammatory responses, providing a novel perspective for preserving dental pulp vitality."

Journal • Dental Disorders • Inflammation • Metabolic Disorders • Oncology • Pain • LA2G7

FOLR2+ tumor-associated macrophages drive metastatic microenvironment remodeling and lymphatic dissemination in colorectal cancer. (PubMed, Cell Signal) - "In vivo, this dual-track cascade was successfully recapitulated: pharmacological inhibition of PLA2G7 with darapladib blunted stromal collagen deposition and primary tumor growth, whereas FOLR2 silencing uniquely suppressed peritumoral lymphangiogenesis and popliteal lymph node metastasis. Bioinformatic analysis further revealed that high co-expression of FOLR2 and PLA2G7 correlates with elevated TIDE scores and increased IC50 values to oxaliplatin and targeted agents, predicting intrinsic immune evasion and therapy resistance. Together, this work establishes FOLR2 as a pivotal regulator of the CRC stroma and suggest that therapeutic strategies targeting the FOLR2/PLA2G7 axis could improve clinical outcomes by disrupting the supportive metastatic niche."

Journal • Colorectal Cancer • Oncology • Solid Tumor • LA2G7

Oxidative stress–associated PLA2 activation drives lysophospholipid dysregulation linked to B cell hyperactivity in systemic lupus erythematosus (EULAR 2026) - "In vivo, lupus-prone MRL/lpr mice received the PLA2 inhibitor darapladib or vehicle for 4 weeks, and serological, immunophenotypic, and renal outcomes were evaluated...Data are presented as mean ± SEM. Statistical significance was assessed using unpaired t-tests."

Oxidative stress • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • SDC1 • TLR5

Lp-PLA2-derived LysoPC drives dendritic cell immunogenic activation and Th17 inflammation in severe asthma. (PubMed, Inflamm Res) - "Importantly, pharmacological inhibition of Lp-PLA2 with darapladib reduced Th17-mediated neutrophilic inflammation in a steroid-resistant asthma model and suppressed DC immunogenicity in vitro. Collectively, our findings define the Lp-PLA2/LysoPC axis as a novel driver of DC-mediated Th17 inflammation, highlighting this pathway as a promising therapeutic target for severe asthma."

Journal • Asthma • Immunology • Inflammation • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • CD4

The Role of Lp-PLA2 in Regulating Macrophage Inflammatory Response in Sepsis-Induced Cardiomyopathy (SCCM 2026) - "Lp-PLA2 regulates macrophage inflammatory response contributing to the occurrence and development of SICM. Inhibiting Lp-PLA2 may improve the prognosis of SICM, and Darapladib could potentially become a therapeutic drug for SICM patients."

Cardiomyopathy • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • CD68 • IL10 • IL1B • IL6 • TNFA

Lysophosphatidylcholine as a mechanistic and therapeutic nexus in atherosclerotic cardiovascular disease. (PubMed, Biomed Pharmacother) - "Although statins, ezetimibe, and PCSK9 inhibitors effectively lower LDL-C, they do not directly target LPC or its downstream inflammatory pathways. Clinical trials of lipoprotein-associated PLA₂ inhibitors (e.g., Darapladib) failed to reduce cardiovascular events, underscoring the complexity of LPC-related signaling. Future therapeutic approaches may involve enhancing lysophospholipase A1 activity or selectively inhibiting LPC production to restore vascular homeostasis. In aggregate, LPC represents a mechanistic bridge between lipid metabolism, vascular inflammation, and thrombosis, underscoring its potential as a biomarker and therapeutic target for residual ASCVD risk."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hematological Disorders • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Thrombosis • Type 2 Diabetes Mellitus • LPL

A novel approach to combat Pseudomonas aeruginosa: repurposing pharmaceuticals for inhibition of phospholipase A. (PubMed, Microbiol Spectr) - "Experimental screening identified that compounds GW4869, darapladib, and rilapladib significantly inhibit Pseudomonas aeruginosa growth by more than 50%. One standout compound, a preclinically studied drug called GW4869, both slows bacterial growth and boosts the effectiveness of the last-resort antibiotic imipenem, suggesting better outcomes with combination treatments. Overall, this research points to the exciting possibility of repurposing human-focused medicines as new antimicrobial agents to help combat the escalating crisis of antibiotic resistance while deepening our insight into how these drugs can influence microbes."

Journal • Infectious Disease

Pla2g7 regulates bone homeostasis via Alox12/12-HETE/Gpr31 signaling axis. (PubMed, Nat Commun) - "Inhibition of Pla2g7 by Darapladib impaired both human and mice osteoclast differentiation, meanwhile, Pla2g7-deficient mice showed higher bone mass and restored the ovariectomy-induced bone loss...Its metabolite 12-HETE (12-hydroxyeicosatetraenoic acid) activated Gpr31 to regulate osteoclast formation via p38 MAPK pathway and mitochondrial energy metabolism. Collectively, our study uncovers an Alox12/12-HETE/Gpr31 axis that regulates Pla2g7-induced osteoclast differentiation, and provides a new insight for osteoporosis treatment."

Journal • Osteoporosis • Rheumatology • LA2G7

Beyond Lipids and Platelets: A Review of Anti-Inflammatory Strategies in Secondary Prevention of Acute Coronary Syndromes. (PubMed, J Clin Med) - "Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways...Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic..."

Journal • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Immunology • Inflammation • Myocardial Infarction • CRP • IL1B • NLRP3

Different eGFR markers and prediction of cardiovascular risk. (PubMed, J Intern Med) - "In chronic coronary syndrome, lower eGFRcys, eGFRcr, and eGFRratio were associated with higher MACE and mortality risk. eGFRcys had the strongest association; eGFRcr and eGFRratio added limited incremental value."

Journal • Atherosclerosis • Cardiovascular • Nephrology • Renal Disease • CST3

PLA2 driven lipid signaling drives ARMS tumorigenic cell properties. (PubMed, Cell Commun Signal) - "PLA2-mediated lipid remodelling supports TIC by promoting linoleic acid-linked lipid signalling. PLA2 inhibition impairs self-renewal, motility, and tumorigenic potential, highlighting it as a promising therapeutic target in ARMS. These findings uncover lipid remodelling as a key metabolic adaptation in ARMS TICs, independent of canonical energy pathways, with implications for targeting the stem-like compartment in pediatric sarcomas."

Journal • Metabolic Disorders • Movement Disorders • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD36 • PPARG • SCARB1

Preliminary assessment of drug repurposing against virus-associated primary effusion lymphoma. (PubMed, J Microbiol Biol Educ) - "We demonstrate proper quantitative interpretation of the data by using ethacrynic acid, quizartinib, and darapladib as examples. We hope that this practical experimental pipeline will spread awareness of the potential of drug repurposing, especially for diseases like PEL that have unmet clinical needs."

Journal • Epstein-Barr Virus Infections • Hematological Malignancies • Kaposi Sarcoma • Lymphoma • Oncology • Sarcoma • Solid Tumor

Activation of the Lp-PLA2/LPC axis triggers endothelial ferroptosis to drive diabetic kidney disease. (PubMed, Free Radic Biol Med) - "We identify the Lp-PLA2/LPC axis as a novel activator of endothelial ferroptosis in DKD. Pharmacological blockade with Darapladib protects the kidney by inhibiting this iron-dependent cell death, providing a mechanistically grounded therapeutic strategy independent of glycemic control."

Journal • Diabetes • Diabetic Nephropathy • Nephrology • Renal Disease • ACSL4 • GPX4 • ICAM1 • NOS3

Targeting Lp-PLA2 inhibits profibrotic monocyte-derived macrophages in silicosis through restoring cardiolipin-mediated mitophagy. (PubMed, Cell Mol Immunol) - "Furthermore, we assessed the efficacy of the Lp-PLA2 inhibitor darapladib in ameliorating silica-induced pulmonary fibrosis in a murine model. Our findings enhance our understanding of silicosis pathogenesis and offer promising opportunities for developing targeted therapies to mitigate fibrotic progression and maintain lung function in affected individuals."

Journal • Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CTSB • LA2G7

Contribution of individual phospholipase A2 enzymes to the cleavage of oxidized phospholipids in human blood plasma‡. (PubMed, J Lipid Res) - "In contrast to truncated species, degradation of full-length OxPLs with > 3 extra oxygens were only minimally inhibited by darapladib. These data provide further insights into the mechanisms regulating circulating levels of OxPLs and lipid mediators generated by PLA2 cleavage of OxPLs, namely oxylipins and LysoPC."

Journal • PRDX6

White blood cell counts can predict 4-year cardiovascular disease risk in patients with stable coronary heart disease: a prospective cohort study. (PubMed, Front Cardiovasc Med) - P3 | "This study included Asian participants (n = 1,933) from the prospective STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, which involved 15,828 patients with stable coronary heart disease with 3-5 years of follow-up on optimal secondary preventive treatment...In patients with stable coronary heart disease, higher WBC counts were associated with a heightened risk for the primary or secondary outcomes. https://clinicaltrials.gov/; Unique identifier NCT00799903."

Journal • Atherosclerosis • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Dyslipidemia • Heart Failure • Hematological Disorders • Myocardial Infarction

Predictive and therapeutic value of lipoprotein-associated phospholipaseA2 in sarcopenia in chronic obstructive pulmonary disease (ERS 2024) - "Darapladib treatment (25 and 50 mg/kg) rescued CS-induced musclemass loss and muscle functions. Darapladib could reverse CS-induced increase of atrogin-1 and MuRF1 expression and activation of inflammatory factors, oxidant enzymes and NF-κB signaling.ConclusionsSerum Lp-PLA2 level was significantly elevated in patients with COPD, especially in sarcopenic patients with COPD, which could be a potential indicator for sarcopenia."

Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Sarcopenia • FBXO32

Lipoprotein-associated phospholipase A2 (Lp-PLA2) : relevant biomarker and therapeutic target? (PubMed, Ann Pharm Fr) - "Despite the disappointing results of clinical trials using the Lp-PLA2 inhibitor darapladib, new pathophysiological, epidemiological and genetic data have enabled the development of new inhibitors. Recent studies also show that Lp-PLA2 is involved in vascular inflammation-related diseases other than atherosclerosis (ischemic stroke, Alzheimer's disease and vascular dementia, diabetes, cancers…), and inhibition of Lp-PLA2 could have beneficial therapeutic in these diseases. This review aims to present new data on Lp-PLA2 and to evaluate its current interest as a biomarker but also as a therapeutic target."

Biomarker • Journal • Review • Alzheimer's Disease • Atherosclerosis • Cardiovascular • CNS Disorders • Dementia • Diabetes • Dyslipidemia • Inflammation • Ischemic stroke • Metabolic Disorders • Oncology

Predictive and therapeutic value of lipoprotein-associated phospholipaseA2 in sarcopenia in chronic obstructive pulmonary disease. (PubMed, Int J Biol Macromol) - "Lp-PLA2 could be a potential indicator for sarcopenia in COPD. Darapladib, an Lp-PLA2 inhibitor, can alleviate CS-induced skeletal muscle dysfunction and represents a potential therapeutic for sarcopenia in COPD."

Journal • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Sarcopenia • FBXO32

Combination of theoretical analysis and experiments: Exploring the role of PLA2G7 in human cancers, including renal cancer. (PubMed, Heliyon) - "Treatment with a PLA2G7 gene inhibitor (darapladib) significantly decreased the viability of ACHN and 786-O cell lines. Additionally, we observed an association between PLA2G7 mRNA levels and various drug sensitivity. Our study suggests that PLA2G7 has the potential to serve as a valuable biomarker and therapeutic target for cancer, particularly in the context of renal cancer."

Journal • Tumor mutational burden • Diffuse Large B Cell Lymphoma • Genito-urinary Cancer • Hematological Malignancies • Kidney Cancer • Lymphoma • Melanoma • Microsatellite Instability • Non-Hodgkin’s Lymphoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • LA2G7 • MSI • TMB

Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma. (PubMed, J Immunother Cancer) - "Macrophage-specific PLA2G7 serves as a novel biomarker capable of prognosticating immunotherapy responsiveness and inhibiting PLA2G7 has the potential to enhance the efficacy of ICB therapy for HCC."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Metabolic Disorders • Oncology • Solid Tumor • CD8 • LA2G7

The lipoprotein-associated phospholipase A2 inhibitor Darapladib sensitises cancer cells to ferroptosis by remodelling lipid metabolism. (PubMed, Nat Commun) - "Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment."

Journal • Metabolic Disorders • Oncology • GPX4

"Remember darapladib? Curious how that reads thru here" (,@BiotechElmo)

"Did darapladib reduce CRP? I don’t think so https://t.co/BYZMEdhtVL" (,@AbbateAntonio)