Cyclic Peptide Drugs: A Review of Past Successes, Current State, and Future Potential

Over 40 cyclic peptide drugs are currently in clinical use, with approximately one new cyclic peptide drug entering the market annually. While the vast majority of approved cyclic peptides derive from natural products (antimicrobials, human peptide hormones), new techniques based on rational design and in vitro evolution now enable de novo development of cyclic peptide ligands for previously untargetable proteins. Several de novo-designed cyclic peptides are already under clinical evaluation.

This is a review article surveying the landscape of cyclic peptide therapeutics, examining approved drugs, those in clinical trials, and emerging development techniques including rational design and in vitro evolution approaches.

Cyclic peptides occupy a unique therapeutic space between small molecule drugs and large biologics, combining the best properties of both. The ability to now design them from scratch — rather than relying solely on natural products — dramatically expands their potential to address diseases where no natural peptide solution exists.

The pharmaceutical industry is increasingly looking beyond traditional small molecules and antibodies. Cyclic peptides represent a growing middle ground — they're large enough to bind challenging protein-protein interaction targets but small enough to potentially be orally bioavailable. The shift from natural product discovery to rational design marks a new era for this drug class.

As a review published in 2017, it does not cover developments from the past several years, a period of rapid advancement in peptide therapeutics. The review focuses on the overview landscape rather than providing detailed clinical efficacy data for individual drugs. The projection of continued growth relies on trends that may be affected by regulatory, manufacturing, or economic factors.