SB225002 / GSK - LARVOL DELTA

Electroacupuncture alleviates inflammatory pain by modulating the CXCL1/CXCR2 signaling axis in the spinal cord dorsal horn of rats. (PubMed, Front Mol Neurosci) - "Intrathecal catheterization was used to administer recombinant CXCL1 or the CXCR2 antagonist SB225002 to study their effects on EA's pain relief...The upregulation of CXCL1 diminishes these effects, whereas the antagonism of CXCR2 amplifies them. Electroacupuncture alleviates chronic inflammatory pain in rats by targeting the CXCL1-CXCR2 signaling axis in the SCDH, reducing CXCL1, CXCR2, and serum IL-1β levels, making it a potential therapeutic target."

Journal • Preclinical • Pain • CXCL1 • CXCR2 • IL1B

CXCL2/CXCR2 pathway regulates CD169high large macrophages to promote progression of malignant pleural effusion from lung adenocarcinoma. (PubMed, Front Med (Lausanne)) - "The effects of CXCL2/CXCR2 signaling on macrophage migration, proliferation, and apoptosis were evaluated using recombinant human CXCL2 and the CXCR2 inhibitor SB225002 in vitro, and the therapeutic effects of CXCR2 inhibition were assessed in vivo...CXCL2/CXCR2 axis promotes macrophage migration and contributes to the accumulation of CD169high macrophages in the MPE microenvironment, thereby facilitating MPE progression. These findings provide new insights into the myeloid-cell regulatory mechanisms underlying MPE and may represent a potential therapeutic strategy for lung cancer-associated MPE."

Journal • Pleural effusion • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Respiratory Diseases • Solid Tumor • CXCR2

Modulation of Brain Injury After Intracerebral Hemorrhage via the Scalp-Skull-Dura Interface in Mice. (PubMed, Stroke) - "To test whether SBM-derived neutrophil migration contributes to neuroinflammation, the CXCR2 (C-X-C motif chemokine receptor 2) antagonist SB225002 was delivered subscalp...SBM may serve as a primary source of pathogenic neutrophils driving neuroinflammation after ICH. Targeting this immune compartment through the scalp-skull-dura interface represents an accessible strategy for mitigating ICH-induced brain injury."

Journal • Preclinical • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • CCL3 • CXCR2

Inhibiting CXCR2 remodels the tumor microenvironment and blunts tumor progression and dissemination of high-grade serous carcinoma. (PubMed, Cancer Res Commun) - "We targeted the migration of MDSCs and neutrophils to the TIME in the ID8-p53null mouse model of HGSC with the CXCR2-selective inhibitor SB-225002 (CXCR2i) alone or in combination with cisplatin. Furthermore, these data reveal new insights into detrimental chemotherapy-induced remodeling of the TIME, which should be investigated as mechanistic targets to improve outcomes in HGSC. Overall, our data demonstrate the clinical relevance and therapeutic potential of targeting CXCR2 to prevent their recruitment of tumor-promoting innate immune cells to the TIME."

Biomarker • Journal • Oncology

The CXCL5/CXCR2 Axis Attenuates Ferroptosis in Intrahepatic Cholangiocarcinoma Through the Positive Feedback Loop Between PTGS2 Transcriptional Activation and Neutrophil Recruitment. (PubMed, Adv Sci (Weinh)) - "Notably, combinatorial treatment with the CXCR2 antagonist SB225002 and ferroptosis inducer Erastin exhibited synergistic antitumor activity in preclinical ICC models. This study provides mechanistic insights into the ferroptosis-immune crosstalk and proposes a novel combinatorial therapeutic paradigm for overcoming treatment resistance in ICC."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CCL2 • CXCL5 • CXCR2 • PACERR • PTGS2

CXCL1-CXCR2 axis inhibits melanogenesis through the suppression of the WNT/β-catenin pathway. (PubMed, Front Immunol) - "Notably, CXCL1 treatment significantly decreased both the expression level and nuclear translocation of β-catenin, a key effector molecule of the WNT signaling pathway, and this effect was effectively reversed by the specific CXCR2 inhibitor SB225002, suggesting that the CXCL1-CXCR2 axis negatively regulates melanogenesis by suppressing the WNT/β-catenin signaling pathway. In summary, this study elucidates a preliminary mechanism by which the CXCL1-CXCR2 axis negatively regulates melanogenesis through inhibition of the WNT/β-catenin signaling pathway, linking inflammatory cytokine networks to the regulatory machinery of melanogenesis. It provides novel perspectives for deciphering the pathogenesis of pigmentary skin disorders and developing therapeutic strategies with combined anti-inflammatory and depigmenting effects."

Journal • Acne Vulgaris • Atopic Dermatitis • Dermatitis • Dermatology • Dermatopathology • Immunology • Psoriasis • CXCL1 • CXCR2 • MITF • Tyrosinase • TYRP1

CXCR2 Blockade Improves Response to Hypo-fractionated Radiation Treatment in a Murine Head and Neck Squamous Cell Carcinoma (HNSCC) Model. (PubMed, Radiat Res) - "Additionally, radiation-induced MDSC chemotaxis was inhibited by SB225002 in a transwell assay. Together, these data suggest CXCR2 inhibition in combination with radiation has therapeutic potential for treatment of HPV-negative HNSCC."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CCL5 • CXCL8 • CXCR2

ANXA11 recruits tumor-associated neutrophils to promote the progression of colorectal cancer. (PubMed, Int Immunopharmacol) - "ANXA11 establishes a pro-tumorigenic positive feedback loop in the CRC microenvironment by regulating the NF-κB/CXCL5/CXCR2 signaling axis. Targeting the ANXA11/CXCR2 axis represents a potential therapeutic strategy for CRC intervention."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA1 • ANXA11 • CDH1 • CXCL5 • CXCR2 • MMP9

The crucial role of RIG-I in upregulating neutrophil CXCR2 expression through the MAPK signaling pathway in viral pneumonia. (PubMed, Respir Res) - "Our study identifies the RIG-I-MAPK-CXCR2 axis as a novel pathogenic signaling cascade that drives dysregulated neutrophilic inflammation in COVID-19, providing a basis for novel therapeutic strategies against respiratory viral infections."

Journal • Acute Lung Injury • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CXCL1 • CXCL8 • CXCR2 • IL6 • TNFA

Interleukin-8 and extracellular vesicles spread senescence in Lymphangioleiomyomatosis microenvironment. (PubMed, Biomed Pharmacother) - "By controlling the translation of SASP factors, the mechanistic Target of Rapamycin (mTOR) is a central regulator of senescence...Here, we demonstrate the possibility to counteract both the autocrine senescence in LAM/TSC cells and senescence induced on PLFs by inhibiting CXCR2, an IL-8 receptor that controls the senescent response to IL-8 stimuli, through the small molecule SB225002...Interestingly, IL-8 is enriched in the LAM/TSC sEVs samples compared to PLFs. Taken together, our results indicate the therapeutic potential to interfere with senescence spreading in lung microenvironment and suggest the employment of molecules targeting senescence as a worthy pharmacological approach for LAM."

Journal • Oncology • Pulmonary Disease • Solid Tumor • CXCL8 • mTOR • TSC2

MLCK platelet ignites neutrophil via mitochondrial transfer to trigger liver injury (EASL 2026) - "Platelet transfusion with Mylk‑deficient platelets, CXCR2 antagonism (SB225002) or small-molecule inhibitor (T4S1820) attenuated inflammation without increasing bleeding risk. Our findings establish MLCK-dependent mitochondrial transfer via TNTs as a novel mechanism of platelet-neutrophil crosstalk that drives NET formation and liver injury. Targeting MLCK or the platelet- neutrophil interaction axis offers a promising and safer therapeutic strategy for inflammatory liver diseases by mitigating inflammation without compromising hemostasis."

Addiction (Opioid and Alcohol) • Cardiovascular • Hematological Disorders • Hepatology • Infectious Disease • Inflammation • Liver Failure • Septic Shock • Thrombosis • CXCR2 • MYLK • PPBP

Loss of astrocytic Bmal1 promotes blood-brain barrier disruption and synaptic dysfunction during systemic inflammation. (PubMed, J Neuroinflammation) - "Accordingly, we generated tamoxifen-inducible, astrocyte-specific Bmal1-knockout (KO) mice...Pharmacological blockade of CXCR2 with SB225002 restored pericyte coverage and attenuated BBB disruption in astrocytic Bmal1 KO mice...Taken together, our findings demonstrate that astrocytic Bmal1 maintains BBB integrity and synaptic stability under inflammatory stress. This work also highlights astrocyte-intrinsic circadian regulation as a critical mechanism linking chemokine production to neurovascular vulnerability."

Journal • Inflammation • Sleep Disorder • ARNTL • BMAL1 • CXCL5 • CXCR2

Intracranial Pressure Spikes Trigger Immune Landscape Changes Promoting Fibrosis Within the Dura Contributing to Chronic Hydrocephalus (IMMUNOLOGY 2026) - "Together, these data define a previously unrecognized dura-based immune mechanism linking transient ICP spikes to chronic CSF outflow failure. This work positions the dura as an active immune organ that senses mechanical stress and mounts maladaptive fibrotic responses, providing new insight into the pathogenesis of post-injury hydrocephalus and immune–mechanical crosstalk at the brain's borders."

CNS Disorders • Fibrosis • Immunology • Vascular Neurology • Ventriculomegaly • CXCR2 • ITGAX • MRC1 • TGFB1

Quantification and pharmacokinetic assessment of SB225002 in mouse: a selective non-peptide CXCR2 antagonist. (PubMed, Bioanalysis) - "The method was utilized to assess PK of SB225002 in mouse, revealing rapid absorption (tmax: 0.4 ± 0.1 h, mean±SD) and metabolism (t1/2: 3.4 2.6 h), along with significant inter-individual variability. This study successfully developed and validated a UHPLC-MS/MS method to determine SB225002 in mouse plasma and first reported its pharmacokinetic parameters in mouse, potentially facilitating further clinical research."

Journal • PK/PD data • Preclinical • CXCR2

Role of CXCL7 in colon cancer cell proliferation (AACR 2024) - "The specificity of CXCL7 actions were examined using a CXCL7 neutralizing antibody (R&D Systems) and an antagonist (SB225002) to C-X-C motif chemokine receptor 2 (CXCR2)...In vivo, CXCL7-expressing HT-29 xenograft tumor weight and PCNA protein levels were 100% and 60% greater, respectively, than vector-expressing tumors (p<0.05). Our study for the first time showed that CXCL7 stimulates colon cancer cell proliferation and enhances aerobic glycolysis."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CXCR2 • PCNA • PPBP

Investigating the role of CXCR2 in NK cells in head and neck cancer (AACR 2025) - "Once tumors reached 50-150mm3, mice were treated by IP injection 3 times per week for 3 weeks with either vehicle, 10mg/kg of CXCR2 inhibitor (SB225002), 1µg/kg of CXCL1, or the combination...Studies are ongoing to examine how NK cell-specific CXCR2 knockout influences HNSCC tumor progression using an NK cell conditional Cxcr2 knockout murine model. These preliminary results suggest that the CXCL1/CXCR2 axis is in fact important for HNSCC tumor control."

Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • CXCL1 • CXCR2 • IFNG • IL1B

p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy. (PubMed, Cell Death Dis) - "Additionally, multiplex analysis to detect senescence-associated secretory phenotype (SASP) after chronic exposure revealed significant upregulation of pathogenic factors such as IL-8 and IL-17, which were attenuated by SB225002 (anti-CXCR2) and secukinumab (anti-IL-17A). Senolytic cocktail of Dasatinib and Quercetin treatment alleviated fibrosis by selectively eliminating senescent cells and improved the survival of healthy cells. This study introduces a novel in vitro model of FECD, revealing the crucial role of cell cycle modulation, senescence and interleukins in the disease advancement and pathogenesis. The findings suggest that targeting senescence and cytokine-driven inflammation could be a promising therapeutic strategy for mitigating FECD progression."

Journal • Fibrosis • Immunology • Inflammation • Ophthalmology • Transplantation • CXCL8 • CXCR2 • IL17A

Exploratory research on therapeutic agents combined with early diagnostic biomarkers for colorectal cancer. (PubMed, Front Pharmacol) - "This study systematically delineates a novel panel of early-detection biomarkers for CRC and identifies SB-225002 as a repurposed candidate therapeutic agent. The integrative strategy combining multi-cohort transcriptomic analysis, drug-repositioning platforms, molecular docking, and experimental validation offers a feasible framework for discovering clinically actionable biomarkers and small-molecule therapies for CRC."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor • ALDH1A1 • ANGPT1 • AOC3 • CNN1 • CXCL3 • FABP4 • MAD2L1 • MCM2 • MELK

Inhibition of CXCR2 improves motor coordination through attenuating white matter lesions in Parkinson's disease models. (PubMed, Biochem Pharmacol) - "Pharmacological inhibition of Cxcr2 with SB225002 promoted OPC differentiation and myelin repair, thereby alleviating WMLs and gait disturbances in MPTP-induced PD mice...We revealed that inhibition of Cxcr2 could promote oligodendrocyte-neuron communication via Synj1-mediated vesicular transport, thereby preserving axonal integrity and neuronal function. In conclusion, this study uncovered the protective role and mechanisms of Cxcr2 inhibition on dopaminergic neurons through attenuating WMLs, highlighting Cxcr2 as a potential therapeutic target for PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease • Solid Tumor

SB225002 Enhances Radiosensitivity in Cervical Cancer via Direct Neutrophil Inhibition and Tumor Cell Suppression. (PubMed, Cancer Lett) - "Meanwhile, SB225002 exerts directly antitumor activity and enhances the radiosensitivity of cervical cancer cells by facilitating DNA double-strand breaks, promoting G2/M phase cell cycle arrest, and inducing apoptosis. In summary, our findings highlight neutrophils inhibition via CXCR2 antagonist as a promising therapeutic strategy to enhance cervical cancer responsiveness to radiotherapy."

Journal • Cervical Cancer • Oncology • Solid Tumor • TGFB1

Involvement of CXCR2 in chronic postsurgical pain occurrence through ERK/p38 activation. (PubMed, Neurosci Lett) - "After intrathecal injection of the CXCR2 antagonist SB225002, the rats' pain threshold increased, accompanied by reduced expression of inflammatory factors and reversal of glial cell activation...Transfection with si-CXCR2 led to decreased expression of p-ERK and p-p38 in microglial cells, along with lower TNF-α and IL-1β levels in the cell supernatant. These results indicate that CXCR2 activates spinal glial cells via the ERK/p38 pathway, promoting neuroinflammation, and CPSP, whereas CXCR2 inhibition counteracts these effects and alleviates CPSP."

Journal • Oncology • Pain • CXCR2 • IL1B • TNFA

IL-8 receptor signaling as a novel target for angiogenic retinopathies. (PubMed, Angiogenesis) - "Likewise, in vivo, in the oxygen-induced retinopathy (OIR) model, either genetic (Cxcr2-/-) or pharmacologic (SB225002) CXCR2 inhibition reduced pre-retinal neovascularization without altering avascularity or VEGF expression. These findings suggest that: (a) Müller cells may link inflammatory and angiogenic responses in the retina, (b) CXCR2 activation may contribute to DR, and (c) CXCR2 inhibitors may be repurposed to reduce pre-retinal neovascularization, a key feature of proliferative DR."

Journal • Age-related Macular Degeneration • Diabetic Retinopathy • Fibrosis • Inflammation • Ocular Inflammation • Retinal Disorders • CXCL1 • CXCL8 • CXCR2 • IL1B • TNFA

Impact of CXCL2 and IL-11 from Rheumatoid Arthritis Synovial Fibroblasts on Angiogenesis and Endothelial Cell Network Formation (ACR Convergence 2025) - "To evaluate the role of VEGF, bevacizumab or ECM without VEGF with/without stimulants were used...SB225002 partially reversed the CXCL2 effect (0.015: 93%; 0.03: 87%; 0.06: 92%)... RASF affect vascularization in vitro and in vivo. CXCL2, IL-11 and RASF-derived supernatants altered the HUVEC network. These findings suggest that CXCL2 as well as IL-11 produced by RASF may significantly contribute to the dysregulated angiogenesis involving ANGPT2 observed in RA."

Fibrosis • Immunology • Inflammation • Inflammatory Arthritis • Osteoarthritis • Rheumatoid Arthritis • Rheumatology • CXCR2 • IL1B • IL6

Repurposing of Chemokine Antagonists for Combined Phase-Resolved Spinal Cord Injury Treatment. (PubMed, Adv Sci (Weinh)) - "The effects of mogamulizumab and chemical antagonists of C-C/C-X-C chemokine receptors TAK-799, SB225002, and MK-7123 on SCI recovery in rodents are further estimated. Here blockade of CCR5 and CXCR1/2 chemokine receptors is shown beneficial for amelioration of acute SCI, whereas anti-CCR4 antibody mogamulizumab readily prevents secondary inflammation in the injured area. Summarizing, the current report claims for a novel combined time-resolved therapeutic modality in SCI treatment, which supports feasibility and motivates off-label clinical evaluation in appropriate cohorts."

Journal • CNS Disorders • Oncology • Orthopedics • CCL2 • CCL22 • CCR4 • CX3CL1 • CXCL1 • CXCR1 • IL2 • IL6 • IL7 • TNFA

Direct Targeting of CXCR2 Receptor Inhibits Neuroblastoma Growth: An In Vitro Assessment. (PubMed, Pharmaceuticals (Basel)) - "Pharmacological inhibition of CXCR2 using SB225002, a selective small-molecule antagonist, was evaluated to determine its effects on cell growth, colony formation, apoptosis, and cell cycle progression in different NB cell lines...This study provides strong evidence for elucidating CXCR2-targeted therapies as an attractive treatment option for NB. These findings support the development of CXCR2-targeted therapies for high-risk NB."

Journal • Preclinical • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • Transplantation • AKT1 • BACH2 • CHEK1 • CXCR2