reparixin (DF 1681Y) / Dompe - LARVOL DELTA

Macrophage-derived IL-1β activates IL1R1high fibroblasts to secrete CXCL1, recruiting pathological CXCR2+ neutrophils and exacerbating early lung injury in severe influenza (ERS 2026) - "Therapeutic intervention with neutrophil‑depleting antibodies, CXCL1‑neutralizing antibodies, or the CXCR2 antagonist Reparixin during the early stage of infection significantly improved severe influenza‑induced lung injury in mice. Collectively, our study delineates a critical IL‑1β–CXCL1 axis coordinated by macrophage–fibroblast crosstalk that orchestrates pathogenic neutrophil recruitment at the early stage of severe influenza."

Infectious Disease • Influenza • Respiratory Diseases • CXCL1 • CXCR2 • IL1B

Reparixin Slows Cancer Cell Migration and Proliferation in Human Head and Neck Cutaneous SCC (AAO-HNSF 2026) - "IL-8 is highly expressed by HNcSCC cells. In our in vitro model, inhibiting IL-8 signaling with reparixin significantly slowed cancer cell migration in all cell lines and cancer cell proliferation at a later timepoint in HNA07. Further investigation into the role of IL-8 within the tumor microenvironment may lead to a novel therapeutic approach for the treatment of cSCC."

Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CXCL8

Spatial characterization of interface dermatitis in cutaneous lupus reveals novel chemokine axis-mediated recruitment of leukocytes that drive disease. (PubMed, Sci Rep) - "Taken together, our data map a pathway from keratinocyte injury to lymphocyte recruitment in CLE via AIM2-Casp8-IL-18-CXCL6-CXCR1 CD14+CD16+ monocyte recruitment, CCL8-CCR2 CD14+ monocyte recruitment, and IFNG/IFNL1-CXCL9/CXCL11-CXCR3 T cell recruitment, and suggest a mechanism by which hydroxychloroquine blocks CCR2+ CD14+ monocyte migration. We also identify reparixin and its derivatives as potential novel inhibitors of CXCR1+ CD14+CD16+ monocyte migration."

Journal • Cutaneous Lupus Erythematosus • Dermatitis • Dermatology • Discoid Lupus Erythematosus • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatology • CASP8 • CCL8 • CCR2 • CD14 • CXCL11 • CXCL6 • CXCL9 • CXCR1 • CXCR3 • IFNG • IFNL1 • IL18

Integrating multi-omics data reveals IL-8 positive cancer-associated fibroblasts as mediators of chemotherapy-induced tumor progression in breast cancer. (PubMed, Front Immunol) - "This study aimed to investigate the role of CAFs exposed to paclitaxel (PTX) or doxorubicin (DOX) in tumor progression and explore the underlying mechanisms...Interestingly, this tumor-promoting effect could be partly reversed by reparixin, an IL-8 receptor inhibitor...Our study suggests that the upregulation of IL-8 in CAFs following PTX or DOX treatment may contribute to chemotherapy-mediated tumor progression. These findings provide potential avenues for improving chemotherapy outcomes."

Journal • Breast Cancer • Oncology • Solid Tumor • CAFs • CXCL8

Hypomethylation of GNA15 Promotes Pancreatic Ductal Adenocarcinoma Progression and Macrophage M2 Polarization via STAT3-CXCL8 Axis. (PubMed, Adv Sci (Weinh)) - "Additionally, high GNA15 expression was associated with Gemcitabine resistance, and the combination of Reparixin and Gemcitabine has shown favorable antitumor efficacy in PDAC. Collectively, we elucidated that GNA15 drives PDAC progression and M2 macrophage polarization via the STAT3-CXCL8 axis and established targeting GNA15-STAT3-CXCL8 as a novel strategy to improve PDAC therapies."

IO biomarker • Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CXCL8 • CXCR1 • CXCR2 • STAT3

Reparixin Slows Cancer Cell Migration and Proliferation in Human Head and Neck Cutaneous Squamous Cell Carcinoma (AHNS 2026) - "IL-8 is highly expressed by HNcSCC cells. In our in vitro model, inhibiting IL-8 signaling with reparixin significantly slowed cancer cell migration in all cell lines and cancer cell proliferation at a later timepoint in HNA07. Further investigation into the role of IL-8 within the tumor microenvironment may lead to a novel therapeutic approach for the treatment of cSCC."

Head and Neck Cancer • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CXCL8

Platelets reprogram neutrophil CXCR2 signaling to uncouple chemokine-driven effector functions (ISTH 2026) - "Functional responses to CXCL2 were measured using chemotaxis assays, extracellular and intracellular reactive oxygen species (ROS) assays, and Ca²⁺ flux analysis in the presence or absence of the CXCR antagonists DF2755A and Reparixin...This platelet-imposed functional and transcriptional reprogramming provides a mechanistic framework for reduced CXCR antagonist efficacy in platelet-rich inflammatory environments and highlights platelet–neutrophil interactions as a critical determinant of chemokine-targeted therapeutic responses. Table or Figure Upload (1) Platelets reprogram neutrophil CXCR2 signaling Page 2 DOI*10.1016/j.rpth.2026.105148"

Inflammation • CXCR2

Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium (MPN-RC 120) (clinicaltrials.gov) - P2 | N=10 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | N=26 ➔ 10 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Enrollment change • Trial primary completion date • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis

Targeting Interleukin-8-Mediated Cellular Crosstalk Reverses Hypertrophic Cardiomyopathy and Cardiac Fibrosis in Noonan Syndrome. (PubMed, Circulation) - "Inhibition of IL-8-CXCR1 signaling by reparixin reversed the pathological effects in cardiac fibroblasts and cardiomyocytes. These data provide evidence that targeting aberrant IL-8-CXCR1 signaling may be an effective therapeutic option for patients with NS-associated hypertrophic cardiomyopathy."

Journal • Cardiomyopathy • Cardiovascular • Fibrosis • Genetic Disorders • Hypertrophic Cardiomyopathy • Immunology • Inflammation • CXCL8 • CXCR1 • LZTR1

Interleukin-8 expression inversely predicts the therapeutic effectiveness of doxorubicin and paclitaxel on triple-negative breast cancer (AACR 2025) - "These findings demonstrated that IL-8 expression could be a useful indicator to predict the responsiveness of TNBC patients who are deciding to receive doxorubicin or paclitaxel therapy."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CXCL8

Mechanistic pathway analysis of PD-L1 upregulation in glioblastoma cells following hypofractionated irradiation (DKK 2026) - "Background: Glioblastoma is the most common and aggressive primary brain tumor in adults, with patient prognosis remaining poor, despite maximal resection followed by radiotherapy and temozolomide...Thus, various signaling-pathway Inhibitors were used (Akt-Inhibitor VIII, c-Met-Inhibitor 1, Cobimetinib, Encorafenib, Erlotinib, m-TOR-Inhibitor 3, Reparixin, Sapanisertib, Vemurafenib)... Targeting this pathway may reduce glioblastoma cell radioresistance and warrants further investigation."

IO biomarker • Late-breaking abstract • Brain Cancer • Glioblastoma • Solid Tumor • CXCR2 • EGFR

FRY Mediates THP1-Driven Ovarian Cancer Invasion Through the PI3K/AKT Pathway. (PubMed, Cells) - "Pharmacological inhibition of the CXCR1/2 axis with reparixin effectively blocked OCM-mediated induction of both NFIX and FRY, suggesting that chemokine signaling initiates this pro-invasive loop. Collectively, these findings suggest that FRY is a macrophage-driven mediator of invasion and underscore its potential relevance in ovarian cancer."

Journal • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • AKT1 • CXCR1 • GLI2

Megakaryocytes engage in emperipolesis with neutrophils and emperipolesis by the immune MK subset leads to efferocytosis and is exacerbated by CXCR1/2 activation in myelofibrosis (ASH 2025) - "In selected experiments, thecocultures were performed with Reparixin (10μM), the inhibitor of CXCR1/CXCR2, or the CD41pos cellswere also labeled with CD53-647 which recognizes the immune-subpopulation...In summary, we conclude that 1) all MK subpopulations engage inemperipolesis with neutrophils but only the immune-MK engage in emperipolesis associated withefferocytosis; 2) due to CXCR1/CXCR2 activation, Gata1low immune-MK are more likely to engage inefferocytosis than the wild-type ones, and this susceptibility decrease with age. In future studies we willinvestigate whether, in contrast to conventional models, MK efferocytosis protects Gata1low mice fromthe development of fibrosis in the bone marrow."

Fibrosis • Immunology • Myelofibrosis • CD53 • CXCL1 • CXCR1 • ITGA2B • ITGAM

Phase II study of reparixin in patients with myelofibrosis. myeloproliferative neoplasms research consortium (MPN-RC) 120 trial (ASH 2025) - P2 | "MPN Research Consortium (MPN-RC) 120 is currently enrolling patients through the MPN-RC clinical sitesthroughout the United States. Clinical Trial Identifier: NCT05835466"

Clinical • P2 data • Fibrosis • Hematological Malignancies • Immunology • Leukemia • Myelofibrosis • CD34 • CXCL8 • CXCR1

Interleukin-8 inhibition by reparixin protects megakaryocytes and alleviates thrombocytopenia in Acute Myeloid Leukemia (ASH 2025) - "Leukemia was validated by bi-daily complete blood count and marrow GFP⁺ blast quantification.The mice then received azacitidine+venetoclax±reparixin until chemotherapy completion andhematologic recovery, with analyses mirroring those in model 1.ResultsIn wild-type C57BL/6 mice, flow cytometric analysis of bone marrow-derived cells revealed that,compared with vehicle control treatment, IL-8 administration markedly reduced the number of CD41⁺MKs (P = 0.0079). This increaseextended to total MK counts and the fraction of terminally differentiated CD41⁺CD42b⁺ MKs, displaying aprotective effect of reparixin on megakaryocytic development and highlighting its potential therapeuticvalue in mitigating thrombocytopenia.ConclusionsThe findings suggest that systemic IL-8 suppresses megakaryocytopoiesis and platelet production,prolonging the bleeding time, similar to AML pathology. In a humanized AML model, reparixin added toazacitidine/venetoclax preserved MK maturation during..."

Acute Myelogenous Leukemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Primary Immunodeficiency • Thrombocytopenia • CXCL8 • CXCR1 • CXCR2 • ITGA2B

NRAS mutation drives excessive netosis and differentiation syndrome in acute promyelocytic leukemia (ASH 2025) - "Background Acute promyelocytic leukemia (APL) is highly curable with all-trans retinoic acid (ATRA) and arsenictrioxide (ATO)...Inhibitors targeting CXCR1/2 (Reparixin), NE(Sivelestat), MEK(Trametinib), PAD4(GSK484), and JAK1/2 (Ruxolitinib) were applied to evaluate their inhibitory effects onNETosis and differentiation...Targeting this pathway with reparixin or sivelestatattenuates NET formation without compromising cell differentiation, offering a promising therapeuticstrategy to mitigate DS-induced tissue damage while preserving anti-leukemic efficacy. These findingsprovide mechanistic insights into NRAS-driven inflammation in APL and support NETs-targeted therapyfor prophylaxis of DS."

Acute Promyelocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Thrombosis • ANXA5 • CXCL8 • CXCR1 • ICAM1 • ITGAM • JAK1 • JAK2 • NRAS • VCAM1

Primary Amine-Catalyzed Enantioselective Fluorination of α-Branched Aldehydes with Low Catalyst Loadings. (PubMed, J Org Chem) - "Furthermore, as a synthetic application, the enantioselective syntheses of fluorine-containing biologically active pharmaceuticals─such as LY50340, α-fluorinated NSAIDs, and α-fluorinated reparixin─were successfully demonstrated. DFT calculations revealed that cumulative steric repulsions among the phenyl groups of NFSI, the enamine, and the catalyst are critical for achieving high enantioselectivity."

Journal

IL-8-Induced Tumor Self-Rampart Spatially Confines Oncolytic Virotherapy in Glioblastoma. (PubMed, Neuro Oncol) - "Glioblastoma mounts a spatial self-protective defense through IL-8-driven TSR formation that restricts oncolytic virus spread. IL-8 functions as both a pharmacodynamic biomarker and a therapeutic target, and its inhibition provides a rational strategy to overcome resistance and optimize GBM virotherapy."

IO biomarker • Journal • Brain Cancer • Fibrosis • Glioblastoma • Infectious Disease • Oncology • Solid Tumor • CXCL8

Fusobacterium nucleatum drives gastric cancer metastasis via Gbp-CypA-NF-κB-mediated CXCL8 crosstalk between tumor cells and mast cells. (PubMed, Cell Commun Signal) - "In summary, this study suggests that Fn contributes to GC progression by promoting tumor cell migration, MCs recruitment and activation. Simultaneously, the enhanced CXCL8-mediated crosstalk between GC cells and MCs plays a vital role in the pro-cancer effect of Fn."

Journal • Gastric Cancer • Oncology • Solid Tumor • CXCL8

Distinctive Alterations in the Emperipolesis between Neutrophils and Megakaryocytes from the Bone Marrow of Gata1low Mice Documented By Time-Lapse Observations (ASH 2024) - "The discovery that the MK from these patients express an IL-8 (CXCL1 in the mouse) signature3, a potent chemo-attractant for Neu4, lead us to discovery that treatment of the Gata1low mouse model with Reparixin, an inhibitor of CXCR1/CXCR2 (the CXCL1 receptors), rescues both fibrosis and pathological MK-Neu emperipolesis in their bone marrow5...6.Huang FY et al. Blood Adv 2022; 6 : 2081."

Preclinical • Fibrosis • Immunology • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • ATG3 • ATG7 • CLEC7A • CXCL1 • CXCL8 • CXCR1 • FPR2 • IL1B • ITGA2B • PTEN • RAB27A • SIRPA • SLC11A1 • TLR2

Integrated multi-omics identifies a CD54+ iCAF-ITGAL+ macrophage niche driving immunosuppression via CXCL8-PDL1 axis in cervical cancer. (PubMed, Mol Cancer) - "Therapeutic intervention using the CXCL8-CXCR1/2 inhibitor reparixin disrupted the CXCL8-PD-L1 axis, reduced PD-L1+ macrophage abundance and enhanced CD8+ T cell cytotoxicity. Notably, combination therapy with PD-L1 blockade demonstrated synergistic efficacy. Collectively, our findings reveal a stromal-immune checkpoint axis orchestrated by CD54⁺ iCAFs and ITGAL⁺ macrophages that underpins immunosuppression in CC, thereby providing a translational rationale for stroma-directed combination therapies that may overcome resistance to current immunotherapies."

IO biomarker • Journal • Cervical Cancer • Oncology • Solid Tumor • CAFs • CCL2 • CD8 • CXCL8 • CXCR1 • ICAM1

Mechanistic pathway analysis of PD-L1 upregulation in Glioblastoma cells following hypofractionated Irradiation (EANO 2025) - "Standard treatment schemes, including surgical resection, temozolomide and radiotherapy, have yielded only modest clinical benefit...This study seeks to identify the signaling pathways responsible for PD-L1 upregulation in GBM after irradiation.Material and We investigated the impact of hypofractionated radiotherapy (2x5Gy) combined with various signaling pathway Inhibitors (Akt-Inhibitor VIII, c-Met-Inhibitor 1, Cobimetinib, Encorafenib, Erlotinib, m-TOR-Inhibitor 3, Vemurafenib and SC79) on the expression profile of the immune checkpoint molecules PD-L1/2 in the murine GBM cell line GL261-luc2 using flow cytometry...Based on the transcriptomic findings, further flow cytometric analyses were conducted to assess the effects of CXCR2 inhibition with Reparixin on PD-L1 regulation... Modulating these pathways post-irradiation may reduce GBM cell radioresistance, necessitating further investigation into potential molecular targets."

IO biomarker • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • CXCR2 • EGFR

Cytokine Blockade Attenuates Inflammation and Improves Depressive Psychopathology After COVID-19: A Naturalistic Observational Study. (PubMed, J Neuroimmune Pharmacol) - "In the present naturalistic observational study we evaluated the possible effect of the cytokine-blocking agents in preventing the development of post-COVID depression in a large sample of survivors also exploring the relationship between post-COVID depressive risk, treatment with cytokine-blocking agents, and innate immune response markers. 588 COVID-19 survivors were included, of them 374 received the best available treatment at the time and 131 received standard treatment combined with cytokine-blocking agents (anakinra, tocilizumab, sarilumab, reparixin and mavrilimumab). Finally, we observed that cytokine-blocking agents' impact on depression was mediated by lowering of systemic inflammation. Our findings indicate potential efficacy of cytokine-blocking agent treatment during the early stages of COVID-19, mitigating post-COVID depressive symptoms by attenuating systemic inflammation. Further investigation through preclinical and clinical studies is..."

Journal • Observational data • CNS Disorders • Depression • Infectious Disease • Inflammation • Novel Coronavirus Disease • Psychiatry

Reparixin in Patients With Myelofibrosis Myeloproliferative Neoplasms Research Consortium (MPN-RC 120) (clinicaltrials.gov) - P2 | N=26 | Recruiting | Sponsor: Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Hematological Disorders • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Thrombocytosis

IMMUNE-MEGAKARYOCYTES ARE RESPONSIBLE FOR THE PATHOLOGICAL INTERLEUKIN-8 DEPENDENT EMPERIPOLESIS WITH NEUTROPHILS ASSOCIATED WITH MYELOFIBROSIS IN GATA1LOW MICE (EHA 2025) - "Selected experiments were performed with Reparixin (10µM), the inhibitor of CXCR1/CXCR2 (expressed at high levels by malignant MK) or the CD53 antibody which recognize the immune MK subpopulation... These data indicate that in the myelofibrosis Gata1low mouse model, MK are enriched for the immune subpopulation which is responsible to activate the CXCL1-dependent pathological emperipolesis which leads to their dead and release of pro-inflammatory cytokines in the microenvironment."

Preclinical • Myelofibrosis • CD53 • CXCL1 • CXCR1 • ITGA2B