- |||||||||| navarixin (MK-7123) / Merck (MSD)
Journal: Angiopoietin-2 regulates the phenotypic switch of vascular smooth muscle cells. (Pubmed Central) - Mar 3, 2025 Lipid peroxidation inhibition by ferrostatin-1 or the IL-8 receptor antagonist navarixin inhibited the Ang-2-induced migration...Ang-2 dysregulation may disrupt spiral artery remodeling and contribute to preeclampsia. Ang-2 may be a novel therapeutic target for the treatment of pregnancy complications affected by incomplete spiral artery remodeling.
- |||||||||| navarixin (MK-7123) / Merck (MSD)
Journal: A Fluorescent Probe Enables the Discovery of Improved Antagonists Targeting the Intracellular Allosteric Site of the Chemokine Receptor CCR7. (Pubmed Central) - Feb 12, 2025 The thiadiazoledioxide 10 was derived from the CCR7 antagonist Cmp2105 by removing a methyl group from the benzamide moiety, while the squaramide 21m was obtained from the CXCR1/CXCR2 antagonist and clinical candidate navarixin by replacing the ethyl substituent by a tert-butyl group to engage a lipophilic subpocket. We show that 10 and 21m qualify to probe CCR7 biology in recombinant and primary immune cells and expect our novel probes to facilitate the design of next-generation intracellular CCR7 ligands.
- |||||||||| navarixin (MK-7123) / Merck (MSD)
Review, Journal: Squaric acid derivatives with cytotoxic activity- a review. (Pubmed Central) - Jan 15, 2025 In this context this review is the first looking into the potential applications of squaric acid derivatives as anticancer therapies. It analyzes experimental studies presented in articles published between 2000 and 2024.
- |||||||||| Xolremdi (mavorixafor) / X4 Pharma, X4P-002 / X4 Pharma, navarixin (MK-7123) / Merck (MSD)
CXCR4 Antagonism Corrects Peripheral Neutropenia and Mature Neutrophil Accumulation in Bone Marrow in a Pharmacological Mouse Model of CXCR2 Loss-of-Function (Grand Hall D (Manchester Grand Hyatt San Diego)) - Nov 6, 2024 - Abstract #ASH2024ASH_1816; Additional clinical manifestations in patients with WHIM syndrome may include warts, hypogammaglobulinemia and lymphocytopenia.1,2 Interestingly, patients with loss-of-function (LoF) variants in CXCR2 display phenotypic features similar to those observed in patients with WHIM syndrome, such as neutropenia, increased infection susceptibility, and myelokathexis.3,4 Mavorixafor, an orally bioavailable CXCR4 antagonist, has demonstrated clinically meaningful increases in absolute neutrophil and lymphocyte counts and concomitant reductions in infections in patients aged 12 years and older with WHIM syndrome, leading to its recent approval by the U.S. Food and Drug Administration.5 Whether CXCR4 antagonist therapy can similarly correct the common pathogenic phenotypes observed in patients with CXCR2 LoF variants as are seen in patients with WHIM syndrome has yet to be determined...Methods Female BALB/c mice (6 mice per group) were dosed with the CXCR2 antagonist navarixin (3 mg/kg) by oral gavage and subsequently the CXCR4 antagonist X4P-002 (10 mg/kg) or vehicle control daily for 7 days, 2 hours after the navarixin dose...Our CXCR2 LoF mice exhibit a phenotype similar to that observed in patients diagnosed with WHIM syndrome, including peripheral blood neutropenia, accumulation of segmented neutrophils, some displaying myelokathexis-like morphology, and an increased M/E ratio in BM, corrected by CXCR4 antagonist therapy. Our data suggest the potential for CXCR4 antagonist therapy to correct neutropenia and normalize clinical phenotypes consistent with WHIM syndrome in patients with CXCR2 LoF variants.
- |||||||||| PF-07054894 / Pfizer, navarixin (MK-7123) / Merck (MSD)
Journal: Development of a NanoBRET Assay Platform to Detect Intracellular Ligands for the Chemokine Receptors CCR6 and CXCR1. (Pubmed Central) - Oct 17, 2024 By means of these studies we identified compound 10, a previously reported tert-butyl analogue of navarixin, as a low nanomolar intracellular CCR6 antagonist. Further, our assay platform clearly indicated intracellular binding of the CCR6 antagonist PF-07054894, currently evaluated in phase I clinical trials for the treatment of ulcerative colitis, thereby providing profound evidence for the existence and the pharmacological relevance of a druggable IABS at CCR6.
- |||||||||| navarixin (MK-7123) / Merck (MSD), Ligand
Journal: Aortic valve calcification is promoted by interleukin-8 and restricted through antagonizing CXCR2. (Pubmed Central) - Jul 30, 2023 This effect may partly result from an inhibition of the GA-induced infiltration of T-cells and macrophages into the xenograft. Overall, these results highlight, for the first time, a significant role for IL-8 in the progression of CAVD by promoting calcification via a CXCR2-- and MMP-12-dependent mechanism that leads to elastin degradation, and identify CXCR2 as a promising therapeutic target for the treatment of CAVD.
- |||||||||| navarixin (MK-7123) / Merck (MSD), Ligand
Journal: Combined inhibition of IL‑6 and IL‑8 pathways suppresses ovarian cancer cell viability and migration and tumor growth. (Pubmed Central) - Mar 29, 2022 In the present study, the efficacy of co‑targeting IL‑6 and IL‑8 in human ovarian cancer cells by bazedoxifene (Baze) + SCH527123 (SCH) treatment was examined...Baze + SCH also inhibited cell migration and invasion, suppressed ovarian tumor growth and inhibited STAT3 and AKT phosphorylation, as well as survivin expression. Therefore, co‑targeting the IL‑6 and IL‑8 signaling pathways may be an effective approach for ovarian cancer treatment.
- |||||||||| navarixin (MK-7123) / Merck (MSD), Ligand
Journal: A Micro-Engineered Airway Lung-Chip Models Key Features of Viral-Induced Exacerbation of Asthma. (Pubmed Central) - Dec 16, 2020 Neutrophil transepithelial migration was greatest when viral infection was combined with IL-13 treatment, whereas treatment with MK-7123, a CXCR2 antagonist, reduced neutrophil diapedesis in all conditions...Our data suggest that IL-13 may impair the hosts' ability to mount an appropriate and coordinated immune response to rhinovirus infection. We also show that the Airway Lung-Chip can be used to assess the efficacy of modulators of the immune response.
- |||||||||| ondansetron / Generic mfg.
Journal: Mild Traumatic Brain Injury Causes Nociceptive Sensitization through Spinal Chemokine Upregulation. (Pubmed Central) - Nov 12, 2020 Also, selective CXCR2 antagonist SCH527123 treatment attenuated mechanical hypersensitivity after mTBI...Our results suggest dual pathways for nociceptive sensitization after mTBI, direct 5-HT effect through 5-HT receptors and indirectly through upregulation of chemokine signaling. Designing novel clinical interventions against either the 5-HT mediated component or chemokine pathway may be beneficial in treating pain frequently seen in patients after mTBI.
- |||||||||| navarixin (MK-7123) / BMS, Merck (MSD), Ligand
Journal: Structural Basis for Allosteric Ligand Recognition in the Human CC Chemokine Receptor 7. (Pubmed Central) - May 13, 2020 We demonstrate how structural data can be used in combination with a compound repository and automated thermal stability screening to identify and modulate allosteric chemokine receptor antagonists. We detect both novel (CS-1 and CS-2) and clinically relevant (CXCR1-CXCR2 phase-II antagonist Navarixin) CCR7 modulators with implications for multi-target strategies against cancer.
- |||||||||| navarixin (MK-7123) / BMS, Merck (MSD), Ligand
Preclinical, Journal: Effect of CXCR2 Inhibition on Behavioral Outcomes and Pathology in Rat Model of Neuromyelitis Optica. (Pubmed Central) - Apr 9, 2019 To reduce immune-mediated damage in a rat model of neuromyelitis optica (NMO) by blocking neutrophil migration using SCH527123, a drug that inhibits CXCR2...This suggests that neutrophils are not centrally involved in the immunopathogenesis of the Lewis rat NMO disease model. CXCR2 inhibitor blocks neutrophil migration into the spinal cord during EAE but does not significantly reduce inflammation or AQP4 lesions in the Lewis rat model of NMO.
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