A series of sulfonamide CCR2 antagonists was identified by high-throughput screening. Management of molecular weight and physical properties, in particular moderation of lipophilicity and study of pK(a), yielded highly potent CCR2 antagonists exhibiting good pharmacokinetic properties and improved potency in the presence of human plasma.
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http://dx.doi.org/10.1016/j.bmcl.2010.04.142 | DOI Listing |
Adv Sci (Weinh)
December 2024
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Intestinal fibrosis, a severe complication of Crohn's disease (CD), is linked to chronic inflammation, but the precise mechanism by which immune-driven intestinal inflammation leads to fibrosis development is not fully understood. This study investigates the role of myeloid-derived suppressor cells (MDSCs) in intestinal fibrosis in CD patients and a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse model. Elevated MDSCs are observed in inflamed intestinal tissues prior to fibrosis and their sustained presence in fibrotic tissues of both CD patients and murine models.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230001, China. Electronic address:
Myocardial infarction (MI) is a leading cause of mortality worldwide, contributing significantly to long-term cardiac dysfunction and heart failure. Effective therapeutic strategies are urgently needed to mitigate the extensive damage caused by MI and subsequent ischemia-reperfusion (I/R) injury. This study investigates the role of the Chemokine receptor 2 (CCR2) in regulating NLRP3-dependent cardiomyocyte pyroptosis following myocardial ischemia-reperfusion (MIR), elucidating its molecular mechanisms.
View Article and Find Full Text PDFInt J Biol Sci
December 2024
Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Macrophages play a crucial role in malignant pleural effusion (MPE), a frequent complication of advanced cancer. While C1q macrophages have been identified as a pro-tumoral cluster, direct evidence supporting the role of C1q-mediated macrophages remains to be elucidated. This study employed global and macrophage-specific knockout mice to investigate the role of C1q in MPE.
View Article and Find Full Text PDFImmun Inflamm Dis
December 2024
College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, China.
Introduction: Acute lung injury (ALI) and its subsequent progression to acute respiratory distress syndrome (ARDS) are severe respiratory conditions. They are marked by rapid lung function deterioration and extensive pulmonary inflammation, often resulting in critical patient outcomes. Alveolar macrophages (AMs) and monocyte-derived macrophages (MDMs) are two distinct subsets of lung macrophages present in the alveoli during ALI.
View Article and Find Full Text PDFMol Psychiatry
November 2024
Department of Regulatory Science for Evaluation & Development of Pharmaceuticals & Devices, Fujita Health University Graduate School of Medical Sciences, Toyoake, Aichi, Japan.
Negative experiences during adolescence, such as social isolation (SI), bullying, and abuse, increase the risk of psychiatric diseases in adulthood. However, the pathogenesis of psychiatric diseases induced by these factors remain poorly understood. In adolescents, stress affects the intestinal homeostasis in the gut-brain axis.
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