SB225002 / GSK - LARVOL DELTA

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

CXCR2 mediates rotenone-induced neuroinflammation and neurodegeneration through neurotrophil infiltration and extracellular traps formation in mice. (PubMed, Int J Biol Macromol) - "Pharmacological inhibition of CXCR2 by SB225002 significantly blunted rotenone-induced dopaminergic neurotoxicity, α-synuclein phosphorylation and motor deficits in mice...Furthermore, degradation of NETs with DNase I suppressed microglial M1 polarization, which was associated with reduced dopaminergic neuronal loss and enhanced motor function in rotenone-exposed mice. Collectively, our results indicate that CXCR2 contributes to rotenone-evoked neuroinflammatory responses and dopaminergic neurodegeneration through promoting neutrophil infiltration and NETs formation, thereby providing experimental support for the pathogenic role of CXCR2 in pesticide-induced neuroinflammation and neurotoxicity."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • CXCL1 • CXCR2 • STAT1

Trans-Organ Early Intervention for Myocardial Infarction Based on Bone Marrow-Homing Biomimetic Nanomedicine. (PubMed, Adv Healthc Mater) - "The findings demonstrate that MMNP@SB225002 confers robust cardioprotection by alleviating post-MI inflammation. This innovative approach delineates a promising remote therapeutic strategy with substantial translational potential, underpinned by its enhanced safety profile."

Journal • Cardiovascular • Fibrosis • Hematological Malignancies • Immunology • Inflammation • Multiple Myeloma • Myocardial Infarction • Oncology

CXCR2 Inhibitor Plus KRAS G12C Inhibitor Remodels Immunosuppressive Tumor Microenvironment in KRAS G12C-Mutant NSCLC? (IASLC-WCLC 2025) - "Hence, co-administration of SB225002, a C-X-C motif chemokine receptor 2 (CXCR2) antagonist targeting PMN-MDSCs, significantly enhanced the inhibitory effect of AMG510 on tumor burden in LLC-bearing mice. Conclusions : The combination therapy demonstrates dual efficacy by potently remodeling the immunosuppressive tumor microenvironment and directly inhibiting tumor cells proliferation. These findings establish a robust experimental foundation for advancing this therapeutic approach into clinical trials."

Biomarker • Tumor microenvironment • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CXCR2 • KRAS

High salt diet intake promotes the induction of experimental autoimmune encephalomyelitis by exacerbating neutrophil infiltration and microglial activation. (PubMed, Eur J Pharmacol) - "The HS diet-induced exacerbation of clinical scores and microglial activation were improved by the pharmacological inhibition of neutrophil chemotaxis with SB225002, a selective CXC chemokine receptor 2 inhibitor. In addition, the pharmacological inhibition of microglial activation with minocycline markedly ameliorated clinical scores of HS diet-fed EAE mice...Blockade of thrombin signaling with vorapaxar, a selective blocker of PAR-1, significantly improved EAE symptoms in the HS diet group. Collectively, our findings suggest that excessive salt intake promotes EAE induction via the activation of neutrophils and microglia in the spinal cord. Dietary salt restriction might be a promising strategy to prevent developing or relapsing MS."

Journal • CNS Disorders • Immunology • Multiple Sclerosis • Solid Tumor

Rad50 restrains intestinal inflammation via the CXCL2-CXCR2 axis in neutrophils (IDDF 2025) - "Furthermore, neutrophil-neutralizing antibody (anti-Ly6G antibody), CXCR2 inhibitor (SB225002) and co-immunoprecipitation assay were used to verify the results in mice or bone marrow-derived neutrophils (BMNs).Results We found reduced RAD50 expression in myeloid cells from inflamed regions of IBD patients...Mechanistically, RAD50 interacted directly with C/EBPβ and negatively regulated C/EBPβ. RAD50 deficiency-induced neutrophil self-activation via the CXCL2-CXCR2 axis and CXCR2 inhibitor could prevent neutrophil migration and inflammation exacerbation in Rad50-deficient BMNs.Conclusions Our findings demonstrated that myeloid cell-specific RAD50 deficiency promotes intestinal inflammation by inducing neutrophil self-activation via the CXCL2-CXCR2 axis, which is mediated through C/EBPβ activation."

Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • CXCR2 • RAD50

Pain-stimulated ultrasound vocalizations and their impact on pain response in mice. (PubMed, PLoS One) - "Their respective inhibitors, loxoprofen and SB225002, significantly improved hyperalgesia induced by sound stress. When sound stress was applied to a mouse model of inflammatory pain in which pain thresholds were restored 14 days after complete Freund's adjuvant administration, prolonged pain and attenuated analgesic effects of loxoprofen were observed. These results suggest that sound stress not only induces inflammation in the brain that causes hyperalgesia but may also be partially responsible for exacerbating inflammatory pain, hence complicating treatment."

Journal • Preclinical • Inflammation • Pain • CXCL1 • PTGS2

The CXCL8-CXCR2 axis promotes M2 macrophage polarization in ovarian cancer via RASGRP4-mediated mTOR-STAT3 signaling. (PubMed, Apoptosis) - "CXCR2 knockdown or inhibition (using SB225002) reduced IL-8-induced upregulation of RASGRP4 mRNA and protein in THP-1 cells...In summary, the CXCL8-CXCR2 axis promotes M2 macrophage polarization via RASGRP4-mediated mTOR-STAT3 signaling in ovarian cancer. Targeting this pathway may be a promising therapeutic strategy to reprogram tumor-associated macrophages and enhance treatment efficacy."

Journal • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • CXCL8 • CXCR2

Type A asparagine synthetase in the zoonotic Cryptosporidium parvum (CpAsnA): Biochemical features and potential as a novel therapeutic target. (PubMed, Int J Parasitol Drugs Drug Resist) - "Four of the 31 TSA hits exhibited lower micromolar activity against CpAsnA enzyme activity, including XD14, SB225002, histone acetyltransferase inhibitor II (HATi-II) and tolcapone. Among the four CpAsnA inhibitors, three displayed lower micromolar in vitro efficacy against the growth of C. parvum in vitro with satisfactory selectivity indices as primary antiparasitic hits. Our data suggest that CpAsnA merits further investigation as a potential drug target in the parasite."

Journal • ASNS

The CXCL1-CXCR2 Axis as a Component of Therapy Resistance, a Source of Side Effects in Cancer Treatment, and a Therapeutic Target. (PubMed, Cancers (Basel)) - "It discusses anti-CXCL1 antibodies and CXCR2 antagonists, including AZD5069, SB225002, SCH-479833, navarixin/SCH-527123, ladarixin/DF2156A, and reparixin, as well as strategies to enhance CXCR2 expression in lymphocytes during adoptive cell therapy to improve immunotherapy outcomes. CXCR2 inhibitors are well tolerated by patients in clinical trials. However, the limited number of studies evaluating these agents in combination with standard chemotherapy precludes any definitive conclusions."

Adverse events • IO biomarker • Journal • Review • Cardiovascular • Oncology • Pain • CXCL1 • CXCL8 • CXCR2

Single-Cell Analysis Reveals that Vitamin C Inhibits Bone Metastasis of Renal Cancer via Cell Cycle Arrest and Microenvironment Remodeling. (PubMed, Adv Sci (Weinh)) - "Combining APM with a CXCR2 antagonist, SB225002, further inhibits bone metastasis progression. This study provides a high-resolution profile of vitamin C's antitumor effects in the bone metastatic microenvironment and supports the rationale for clinical trials of vitamin C in bone metastatic RCC."

Journal • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CXCR2

Induction of cell death by the CXCR2 antagonist SB225002 in colorectal cancer and stromal cells. (PubMed, Biomed Pharmacother) - "Interestingly, the same response in terms of inhibition of cell viability also occurs in the stromal compartment (normal fibroblasts): however, in this compartment, the G2/M block is non reversible, hence leading to non-apoptotic cell death. These findings suggest that SB225002 could be a potential therapeutic agent in colorectal cancer, by affecting not only cell viability, but also tumor-stroma interactions."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CXCR1 • CXCR2

TGFB1/CXCL5 axis regulation by LCN2 overexpression: a promising strategy to inhibit colorectal cancer metastasis and enhance prognosis. (PubMed, Front Immunol) - "Combined treatment with the SB431542 and the SB225002 significantly attenuated LCN2-related CRC metastasis. Targeting the LCN2/TGFB1/CXCL5 axis emerges as a promising therapeutic strategy for managing LCN2-related metastatic CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CXCL5 • LCN2 • TGFB1

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

Inhibition of IL-8/CXCR2 signaling axis prevents tumor growth and metastasis in triple negative breast cancer cells. (PubMed, Pharmacology) - "Our results underscore the significant role of the IL-8/CXCR2 signaling axis in the metastasis of TNBC and suggest that CXCR2 inhibitors such as SB225002 may be promising therapeutic agents for TNBC patients."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BCL2 • BIRC5 • CXCL8 • CXCR1 • CXCR2 • HER-2 • HIF1A • XIAP

GLIA-LIKE CELLS FROM HUMAN MESENCHYMAL STEM CELLS AMELIORATE COGNITIVE DEFICITS IN A MOUSE MODEL OF VASCULAR COGNITIVE IMPAIRMENT AND DEMENTIA (ADPD 2025) - "Additionally, the CXCR2 antagonist SB225002 treatment group was intraperitoneally administered for 5 days... These findings suggest that ghMSCs can enhance neuronal regeneration and tight junction restoration, thereby contributing to cognitive improvement in an animal model of VCID. Furthermore, we found that CXCR2 is crucial in the mechanism of action of ghMSCs."

Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Ischemic stroke • CXCR2

Neutrophil damage liver regeneration after hepatectomy in MASLD mice through Neutrophil extracellular traps (APASL 2025) - "Neutrophils impaired liver regeneration after hepatectomy in MASLD mice by producing NETs. Inhibition of neutrophils migration by SB225002 and inhibition of NETS production by GSK484 promoted liver regeneration in MASLD mice."

Preclinical • Hepatology • Liver Failure • Metabolic Dysfunction-Associated Steatotic Liver Disease • CXCL1 • CXCR2

IL-8-NF-κB-ALDH1A1 loop promotes the progression of intrahepatic cholangiocarcinoma. (PubMed, Hepatol Commun) - "IL-8-derived tumor cells could upregulate ALDH1A1 expression by activating the NF-κB signaling pathway, promoting tumor progression. Upregulation of ALDH1A1 could activate NF-κB to promote IL-8 secretion, forming a positive feedback loop to promote tumor invasiveness and cell stemness in ICC."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • ALDH1A1 • CXCL8 • CXCR2

Interleukin 1 β suppresses bile acid-induced BSEP expression via a CXCR2-dependent feedback mechanism. (PubMed, PLoS One) - "Consistently, inhibition of CXCR2 with the inhibitor SB225002 significantly attenuated of the inhibitory effect of IL-1β on BSEP expression. These data suggest that part of the cholestasis-inducing effect of IL-1β is mediated via a CXCR2-dependent feedback mechanism."

Journal • Cholestasis • Hepatology • Infectious Disease • Inflammation • Septic Shock • CXCL1 • CXCR2 • IL1B