dapansutrile (OLT1177) / Olatec Therap - LARVOL DELTA

Dapansutrile mitigates methotrexate-induced hepatotoxicity in rats: roles of inflammation, oxidative stress, pyroptosis, and autophagy. (PubMed, Front Pharmacol) - "DAPA suppressed oxidative stress, attenuated inflammatory cytokine production, inhibited inflammasome-mediated pyroptosis, and restored autophagic balance. Collectively, these findings demonstrate that DAPA confers robust hepatoprotection against MTX-induced toxicity through coordinated modulation of inflammatory, oxidative, pyroptotic, and autophagic pathways."

Journal • Preclinical • Hepatology • Inflammation • Liver Failure • IL18 • IL1B • MYD88 • NLRP3 • TLR4

Targeting NLRP3 inflammasome to mitigate chemotherapy-induced cardiotoxicity: advances in selective inhibitors and natural modulators. (PubMed, Mol Biol Rep) - "This broader perspective illustrates the wider impact of inflammasome-mediated pathophysiology in chemotherapy-induced cardiac failure and goes beyond traditional doxorubicin-centered treatments. The review also provides an overview of the therapeutic landscape of selective NLRP3 inhibition, including natural modulators such as oridonin, curcumin, resveratrol, honokiol, and flavonoids, as well as synthetic inhibitors such as MCC950, CY-09, OLT1177 (dapansutrile), and tranilast...Despite encouraging preclinical findings, translational challenges remain, including long-term safety assessment. Modulation of NLRP3 inflammasome activation has emerged as a potential intervention to limit chemotherapy-induced cardiac injury and dysfunction in cardio-oncology."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders • Oncology • IL18 • IL1B • NLRP3 • TXNIP

DAPA-PD: A Trial to Test the Use of Dapansutrile, an Anti-inflammatory Medication, in People With Parkinson's Disease (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Cambridge University Hospitals NHS Foundation Trust | Trial completion date: Feb 2028 ➔ Jun 2028 | Trial primary completion date: Aug 2027 ➔ May 2027

Trial completion date • Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease • CRP

OLT1177 (Dapansutrile) inhibits Gasdermin D-dependent IL-1β Release and Pyroptotic Cell Death in Bone Marrow-derived Macrophages. (PubMed, bioRxiv) - "Overall, our study demonstrates that OLT1177 prevents IL-1β release from BMDMs by inhibiting caspase-1 and the conversion of (GSDMD) into its active N-terminal fragment (GSDMD-N). This study thus supports the concept that orally administered OLT1177 can be used to prevent local as well as systemic inflammation in humans."

Journal • Infectious Disease • Inflammation • CASP1 • CCL3 • IL1B • MPO • NLRP3

Decoding neuroinflammation: the critical role of NLRP3 inflammasome in Alzheimer's disease. (PubMed, Inflammopharmacology) - "Furthermore, the review assesses preclinical and clinical research targeting NLRP3 and its upstream regulators, emphasizing potential treatment options as Simufilam, MCC950, OLT1177, and CY-09. This work highlights the therapeutic potential of the inflammasome and promotes the development of targeted anti-inflammatory treatments to ameliorate AD pathology by elucidating the molecular mechanisms linking NLRP3 to AD progression."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Metabolic Disorders • IL18 • IL1B • NLRP3 • TLR4

Dapansutrile alleviates sepsis-induced cardiac injury by modulating NF-кB-induced inflammatory response and TXNIP/NLRP3/ GSDMD-mediated pyroptosis. (PubMed, Tissue Cell) - "Additionally, DPAP ameliorated the increase in the pyroptotic marker, N-terminal domain of gasdermin D (GSDMD-N), induced by LPS injection. Collectively, our findings suggest that DAPA exerts cardioprotective effects by inhibiting the NF-κB/cytokine and TXNIP/NLRP3/caspase-1/IL-1β/GSDMD-N signalling pathways, positioning it as a potential therapeutic candidate for septic cardiac injury."

Journal • Cardiovascular • Infectious Disease • Inflammation • Septic Shock • IL1B • NLRP3 • TXNIP

A Narrative Review of the Pharmacological Potential of Dapansutrile, a Selective NLRP3 Inflammasome Inhibitor. (PubMed, J Biochem Mol Toxicol) - "NLRP3 inflammasome composition, downstream pathways, and inhibitor development offer the potential for treating inflammation-related diseases. Several inhibitors have emerged and are currently in clinical trials, with over 10 having completed trials and recruiting participants."

Journal • Review • Immunology • Inflammation • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology • NLRP3

Biological Therapies for Urate Lowering and Inflammation Control in Gout Management. (PubMed, J Inflamm Res) - "Pegloticase achieves sustained urate reduction in refractory gout. Concomitant immunomodulatory therapy using methotrexate or mycophenolate substantially improves response rates by mitigating antidrug antibody formation...Anakinra accumulated extensive off-label evidence over two decades without formal approval, while rilonacept faced regulatory rejection in 2012 despite demonstrating efficacy. Canakinumab received Food and Drug Administration (FDA) approval in August 2023 after its initial rejection in 2011, becoming the first biologic formally indicated for gout in the United States...OLT1177 has advanced through clinical development after incorporating safety lessons from the hepatotoxicity experience associated with MCC950...Remaining challenges include immunogenicity management, treatment costs that limit accessibility, and incomplete long-term safety characterization. Future progress depends on refining patient selection through predictive biomarkers and..."

Journal • Review • Chronic Kidney Disease • Gout • Immunology • Inflammation • Inflammatory Arthritis • Nephrology • Renal Disease • Rheumatology • Solid Organ Transplantation • Transplantation • NLRP3

Olatec Therapeutics...announced that two patients have been randomized in a 12-month clinical trial, named DAPA-PD, for the treatment of Parkinson's disease (PD). (Newswise) - "This first 12-month duration study with an NLRP3 inhibitor in PD is designed to evaluate the safety and tolerability of dapansutrile treatment in subjects with early-stage PD, as well as its impact on inflammation, pharmacokinetics, and preliminary efficacy. Key endpoints include changes in systemic and neuroinflammatory biomarkers (e.g., C-reactive protein, inflammatory cytokines, and PET brain imaging). Clinical outcomes will also be assessed."

Trial status • Parkinson's Disease

NLRP3 SELECTIVE ANTAGONIST REDUCES ANTHRACYCLINE+/-TRASTUZUMAB INDUCED CARDIOTOXICITY THROUGH INHIBITION OF FERROPTOSIS AND ACTIVATION OF PAMPK PATHWAYS IN HIPSC-CMS CELLS (ACC 2026) - "The overall picture of the study warrent on the use of dapansutrile in primary prevention of anthracycline and trastuzumab induced cardiovascular events in preclinical and clinical models of CTRCD."

Breast Cancer • Cardiovascular • HER2 Breast Cancer • HER2 Positive Breast Cancer • Solid Tumor • CSF2 • HER-2 • IFNG • IL10 • IL12A • IL17A • IL1B • IL2 • IL4 • IL6 • MYD88 • NLRP3 • RELA • TLR4 • TNFA

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Olatec Therapeutics LLC | Trial completion date: Aug 2026 ➔ Jan 2027 | Trial primary completion date: Jul 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

Targeting NLRP3 inflammasome: a novel strategy for improving immune checkpoint inhibitor-associated pneumonitis. (PubMed, Transl Lung Cancer Res) - "Therapeutic interventions with NLRP3 inflammasome inhibitors (MCC950 and dapansutrile) and a macrophage-depleting agent (clodronate liposomes) were evaluated by micro-computed tomography (CT), histopathology, and serum inflammatory cytokine assays. The findings revealed: (I) significant upregulation of NLRP3 inflammasome pathway-related genes and downstream factors (IL-1β, IL-18) in CIP mouse lungs, alongside increased macrophage infiltration; (II) pneumonitis injury was markedly alleviated and serum inflammatory cytokine levels were reduced by both NLRP3 inflammasome inhibition and macrophage depletion; (III) dapansutrile downregulated NLRP3 expression via inhibition of the NF-κB pathway; (IV) enriched macrophage subpopulations (Mac-IL1B) expressing high levels of NLRP3 were identified in CIP patients. This study provides the first evidence that NLRP3 inflammasome activation constitutes a key upstream mechanism in CIP pathogenesis, offering novel therapeutic strategies..."

Checkpoint inhibition • IO biomarker • Journal • Inflammation • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor • IL18 • IL1B • NLRP3

DAPA-PD: A Trial to Test the Use of Dapansutrile, an Anti-inflammatory Medication, in People With Parkinson's Disease (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Cambridge University Hospitals NHS Foundation Trust | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2025 ➔ Feb 2026

Enrollment open • Trial initiation date • CNS Disorders • Movement Disorders • Parkinson's Disease • CRP

Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: Marc Donath | Trial completion date: Jul 2026 ➔ Jul 2028 | Trial primary completion date: Jul 2026 ➔ Jul 2028

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP

A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=26 | Active, not recruiting | Sponsor: April Salama, M.D. | Recruiting ➔ Active, not recruiting | Trial completion date: Apr 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2026 ➔ Apr 2027

Enrollment closed • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

A Combination of VX765 and OLT1177 Reduced Brain Injury after Intracerebral Haemorrhage via Inhibiting Inflammasome Activation. (PubMed, Folia Biol (Praha)) - "Notably, the combination of OLT1177 and VX765 further attenuated brain injury after ICH by inhibiting inflammasome activation. The combination of OLT1177 and VX765 thus provided enhanced protection against brain injury by inhibiting inflammasome activation, suggesting that OLT1177 in combination with VX765 might serve as a promising therapeutic strategy for the treatment of ICH."

Journal • Cardiovascular • CNS Disorders • Inflammation • Vascular Neurology • CASP1 • IL1B • NLRP3

Immunometabolic disorders in type 2 diabetes mellitus mediated by NLRP3 inflammasome activation and methods of pharmacological correction thereof (PubMed, Probl Endokrinol (Mosk)) - "Given the role of interleukin-1β (IL-1β) in the inflammation associated with type 2 DM, anti-IL-1 therapies such as anakinra, canakinumab and gevokizumab are being investigated in both experimental models of DM and clinical trials. Among the inhibitors of NLRP3 inflammasome activation, MCC950, OLT1177, CY-09 are the most studied, but none of the compounds in this group are currently used in clinical practice. The aim of this review is to assess the role of the NLRP3 inflammasome in the pathogenesis of type 2 diabetes, as well as the potential of inflammasome pathway inhibitors as promising therapeutic agents."

Journal • Review • Diabetes • Infectious Disease • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • IL1B • NLRP3

Dapansutrile preserves pancreatic beta-cell function by regulating insulin vesicle membrane fusion and mitochondrial homeostasis. (PubMed, Diabetes Obes Metab) - "DAPA targets the NLRP3 inflammasome in pancreatic beta cells of diabetic mice to preserve function, maintain mitochondrial homeostasis and offer potential avenues for diabetes management strategies."

Journal • Diabetes • Metabolic Disorders • Transplantation • Type 1 Diabetes Mellitus • NLRP3

Pyroptosis in Ischemic Stroke: Roles, Mechanisms, and Therapeutic Strategies. (PubMed, Restor Neurol Neurosci) - "Pharmacological inhibition of inflammasomes (MCC950, CY-09, OLT1177), caspases (VX-765, Ac-YVAD-CMK), or gasdermins (disulfiram, necrosulfonamide) markedly reduces IL-1β/IL-18 release and preserves neurovascular integrity in preclinical models, highlighting pyroptosis as a therapeutically tractable axis in ischemic stroke. Despite these advances, challenges remain in defining temporal-cellular specificity and achieving clinical translation. Integrating single-cell multi-omics, spatial imaging, and nanocarrier-based delivery systems may enable precise, phase-adaptive modulation of pyroptosis, transforming destructive inflammation into controlled neurovascular recovery."

Journal • Review • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Metabolic Disorders • Vascular Neurology • CASP4 • IL18 • IL1B • NLRP3 • STING • TXNIP

A Hidden Pathway to a Major Concern: The Role of Pyroptosis in Inducing Myocardial Infarction Reperfusion Injury and Emerging Therapeutic Targets. (PubMed, Cureus) - "Trials of agents like cyclosporine A and remote ischemic conditioning have yielded mixed results...MCC950, OLT1177, and VX-765 are NLRP3, caspase-1, and GSDMD inhibitors that decrease the infarct size in mice prior to use in humans. The clinical IL-1β antagonist canakinumab was effective in reducing recurrent events in the CANTOS (Cardiovascular Risk Reduction Study (Reduction in Recurrent Major CV Disease Events)) trial...Focusing on this can help expand our aim to look for more potential therapeutics. The re-purposing of existing drugs, such as colchicine and disulfiram, and the development of new, specific NLRP3 inhibitors represent a promising pipeline toward finally achieving clinically relevant cardioprotection that enhances the prognosis in patients suffering from myocardial infarction."

Journal • Review • Cardiovascular • Inflammation • Myocardial Infarction • Reperfusion Injury • IL18 • IL1B • NLRP3

The NLRP3 inflammasome inhibitor OLT1177 attenuates retinal neovascularization and microglial inflammation with neuroprotective effects. (PubMed, Int Immunopharmacol) - "Microglial activation and NLRP3 inflammasome-associated microglial inflammation were alleviated in the OLT1177-treated mice. In conclusion, NLRP3 inflammasome activation and microglial inflammation occurred in ischemic retinopathies and the inhibitor OLT1177 was well-tolerated and beneficial in attenuating RNV and preventing neuronal death in the retinas of OIR mice, which indicated that OLT1177 might be a promising treatment option for ischemic retinopathies."

Journal • Age-related Macular Degeneration • Diabetic Retinopathy • Inflammation • Retinal Disorders • NLRC5 • NLRP3

Dapansutrile in multidisciplinary therapeutic applications: mechanisms and clinical perspectives. (PubMed, Front Pharmacol) - "Furthermore, dapansutrile exhibits synergistic effects when combined with agents such as lonafarnib or immune checkpoint inhibitors, enhancing anti-inflammatory and anti-tumor responses. This review consolidates evidence on dapansutrile's molecular mechanisms, therapeutic applications, and biosafety, highlighting its potential as a novel, well-tolerated, and versatile anti-inflammatory agent. Future research should focus on optimizing its delivery, particularly to the central nervous system, and leveraging artificial intelligence to predict effective drug combinations."

Journal • Review • Cardiovascular • CNS Disorders • Dental Disorders • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Arthritis • Inflammatory Bowel Disease • Oncology • Periodontitis • Rheumatology • IL18 • IL1B • NLRP3

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Olatec Therapeutics LLC | Trial completion date: Dec 2025 ➔ Aug 2026 | Trial primary completion date: Nov 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

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

Inflammasomes as Potential Therapeutic Targets to Prevent Chronic Active Viral Myocarditis-Translating Basic Science into Clinical Practice. (PubMed, Int J Mol Sci) - "Additionally, we discuss both novel and established therapeutic strategies targeting inflammatory and anti-fibrotic mechanisms, including IL-1 receptor blockers (anakinra, canakinumab), NOD-like receptor protein 3 (NLRP3) inhibitors (colchicine, MCC950, dapansutrile, INF200), NF-κB inhibitors, and angiotensin receptor-neprilysin inhibitors (ARNI), as well as microRNAs. Our aim is to emphasize the clinical importance of early identification of patients at risk of transitioning from acute to chronic inflammation, elucidate the role of inflammasomes, and present emerging therapies that may improve outcomes by balancing effective pathogen clearance with limitation of chronic cardiac damage."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • IL18 • IL1B • NLRP3