Small Molecules in Development for the Treatment of Sepsis: Insights into Drug Targets and Molecular Mechanisms

Sepsis is a life-threatening syndrome driven by a dysregulated host response to infection, characterized by excessive inflammation, coagulation imbalance, and endothelial dysfunction, often progressing to multiple organ dysfunction and death. Small-molecule agents have emerged as promising therapeutic candidates by targeting key pathogenic pathways, including microbial clearance, immunomodulation, restoration of coagulation homeostasis, endothelial protection, and metabolic support. We summarize recent progress in small-molecule therapies for sepsis, focusing on their molecular targets, structural characteristics, pharmacological effects, and mechanisms of action. Although many candidates have shown encouraging results in preclinical and early clinical studies, their safety and efficacy remain to be confirmed in large-scale trials. To date, no small-molecule drug specifically targeting the core pathophysiology of sepsis has been approved, and most compounds are still under development.