Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress toward addressing long-standing bioavailability challenges. Beyond delivery, we examine how peptide and cyclization types, along with specific chemical modifications, relate to administration routes, therapeutic indications, and molecular targets. We also assess physicochemical properties to understand how molecular features influence developability. Together, these insights provide a comprehensive view of the evolving cyclic peptide landscape and emerging principles guiding their future development.