Over 40 cyclic peptide drugs are clinically approved, with macrocyclization strategies addressing the stability and cell permeability challenges that limit linear peptides.
40+ approvedcyclic peptide drugs already on the market, with the field rapidly expanding through new discovery platforms
What the researchers found
Cyclic peptides offer a middle ground between small molecule drugs and large biologics. Their ring structure gives them better cell permeability and metabolic stability compared to linear peptides, while still allowing them to bind large protein surfaces that small molecules cannot reach.
More than 40 cyclic peptide drugs have reached clinical approval, most derived from natural products. Newer approaches including rational design, mRNA display, phage display, and DNA-encoded libraries are creating cyclic peptides against targets that nature never addressed.
The review covers multiple macrocyclization strategies including disulfide bonds, lactam bridges, hydrocarbon stapling, and click chemistry, each with different trade-offs in terms of stability, permeability, and ease of synthesis.
Why it matters
Many important disease targets involve protein-protein interactions that small molecule drugs cannot disrupt. Cyclic peptides can reach these targets while being more stable and cell-permeable than linear peptides.
This review provides a roadmap of current strategies, helping researchers choose the right approach for their specific target.
The numbers in context
40+ clinically approved cyclic peptide drugs; multiple macrocyclization strategies surveyed
How the study worked
This is a comprehensive literature review covering cyclic peptide drug development, including approved drugs, clinical candidates, and discovery platforms. It surveys macrocyclization chemistry, structure-activity relationships, and in vitro evolution methods.
Who was studied
N/A (literature review)
What this study cannot tell us
As a review article, this does not present new experimental data. The strategies described vary widely in their stage of development, from approved drugs to early-stage concepts.
The review may not capture the most recent advances published after its completion.
How to read the evidence
Not applicable (comprehensive review). Summarizes clinical data across dozens of approved drugs and ongoing research.
When this study was published
Published in 2020. The cyclic peptide drug pipeline has continued to grow substantially since this review.
The bigger picture
Many important disease targets are 'undruggable' by small molecules but too expensive to target with antibodies. Cyclic peptides fill this gap, and the field is accelerating with new discovery platforms, improved cyclization chemistry, and better understanding of cell permeability rules.
Questions still open
- Which macrocyclization strategy produces the best cell permeability?
- Can cyclic peptides achieve oral bioavailability consistently?
- What are the manufacturing cost advantages over antibodies?
Common questions
What makes cyclic peptides different from regular drugs?
Are cyclic peptide drugs expensive?
Read the original research
A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies.
Medicinal research reviews, 40(2), 753-810
Citation
Jing, Xiaoshu; Jin, Kang. (2020). A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies.. Medicinal research reviews, 40(2), 753-810. https://doi.org/10.1002/med.21639