SCH 546738 / Merck (MSD) - LARVOL DELTA

A Comparative Study of the Effects of Nine CXCR3 Antagonists on Macrophage Function and the Treatment of Acute Lung Injury. (PubMed, Front Biosci (Landmark Ed)) - "All nine CXCR3 antagonists were shown to influence macrophage function to varying degrees and confer protective effects against ALI. These finding suggest that comparative evaluation of CXCR3 antagonists and the discovery of novel compounds may provide new therapeutic targets for the treatment of inflammatory diseases."

Clinical • Journal • Acute Lung Injury • Acute Respiratory Distress Syndrome • Dental Disorders • Immunology • Inflammation • Periodontitis • Pulmonary Disease • Respiratory Diseases • Rheumatology • CXCL10 • CXCR3

Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment. (PubMed, Cancer Immunol Immunother) - "Moreover, we found that CD8+ T cells were recruited by CXCL10 in vitro, whereas SCH546738, an inhibitor of CXCR3, inhibited T cell migration and splenocytes-mediated anti-tumor effect...In conclusion, this study revealed that CXCL10 expression is correlated with PD-L1 in tumors, sharing the same signaling pathway and associating with better immunotherapeutic efficacy. Further evidence in the syngeneic tumor models demonstrated that immunotherapy-sensitive CT26 intrinsically exhibited higher IFNα and CXCL10 compared to immunotherapy-resistant LL/2 to recruit and activate CD8+ T cells in the tumor microenvironment, exhibiting "hot tumor" characteristic of sensitizing αPD-L1 immunotherapies."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCL10 • CXCR3 • IFNA1 • IFNG • IRF1 • LAMP1 • STAT1

Structural insights into the activation and inhibition of CXC chemokine receptor 3. (PubMed, Nat Struct Mol Biol) - "SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development."

Journal • CD4 • CXCL11 • CXCL9 • CXCR3

Ligand activation induces different conformational changes in CXCR3 receptor isoforms as evidenced by plasmon waveguide resonance (PWR). (PubMed, Sci Rep) - "...Using various concentrations of SCH546738, a CXCR3 specific inhibitor, we demonstrated that low SCH546738 concentrations (≤1 nM) efficiently inhibited CXCR3-A but not CXCR3-B's conformational change and activation. This was confirmed by both, biophysical and biological methods. Taken together, our study demonstrates differences in the behavior of CXCR3-A and CXCR3-B upon ligand activation and antagonist inhibition which may be of relevance for further studies aimed at specifically inhibiting the CXCR3A isoform."

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