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Review
. 2023 Jul 12;16(7):996.
doi: 10.3390/ph16070996.

Cyclic Peptides in Pipeline: What Future for These Great Molecules?

Lia Costa  1   2 , Emília Sousa  1   2 , Carla Fernandes  1   2
Affiliations
Review

Cyclic Peptides in Pipeline: What Future for These Great Molecules?

Lia Costa et al. Pharmaceuticals (Basel). .

Abstract

Cyclic peptides are molecules that are already used as drugs in therapies approved for various pharmacological activities, for example, as antibiotics, antifungals, anticancer, and immunosuppressants. Interest in these molecules has been growing due to the improved pharmacokinetic and pharmacodynamic properties of the cyclic structure over linear peptides and by the evolution of chemical synthesis, computational, and in vitro methods. To date, 53 cyclic peptides have been approved by different regulatory authorities, and many others are in clinical trials for a wide diversity of conditions. In this review, the potential of cyclic peptides is presented, and general aspects of their synthesis and development are discussed. Furthermore, an overview of already approved cyclic peptides is also given, and the cyclic peptides in clinical trials are summarized.

Keywords: bioactivity; clinical trials; cyclic peptides; cyclization; pipeline.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Evolution of approved peptide drugs over the years.
Figure 2
Figure 2
Comparison between approved cyclic and linear peptides (A). Routes of administration of approved peptides (B). IV: Intravenous; IM: Intramuscular; SC: Subcutaneous.
Figure 3
Figure 3
Diverse peptide cyclization methods. (A) Cyclization in solution; (B) Cyclization by native chemical ligation; (C) Cyclization by Ser/Thr ligation approach; (D) Cyclization by KAHA ligation approach; (E) Cyclization by Staudinger’s ligation approach; (F) On-resin cyclization; (G) Enzyme-mediated cyclization; (H) CyClick cyclization; (I) Cyclization by formation of a triazene bond; (J) Cyclization of propargylated peptides through imine formation mediated by gold.
Figure 4
Figure 4
Schematic representation of the phage display strategy.
Figure 5
Figure 5
Available structures of the cyclic peptides currently in clinical trials as new chemical entities.
Figure 5
Figure 5
Available structures of the cyclic peptides currently in clinical trials as new chemical entities.
Figure 6
Figure 6
Structures of approved cyclic peptides currently in clinical trials for other diseases.
Figure 7
Figure 7
Structures of cyclic peptides in clinical trials whose development has been interrupted.
See this image and copyright information in PMC

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