Cyclic peptide drugs approved in the last two decades (2001-2021)

Abstract

In contrast to the major families of small molecules and antibodies, cyclic peptides, as a family of synthesizable macromolecules, have distinct biochemical and therapeutic properties for pharmaceutical applications. Cyclic peptide-based drugs have increasingly been developed in the past two decades, confirming the common perception that cyclic peptides have high binding affinities and low metabolic toxicity as antibodies, good stability and ease of manufacture as small molecules. Natural peptides were the major source of cyclic peptide drugs in the last century, and cyclic peptides derived from novel screening and cyclization strategies are the new source. In this review, we will discuss and summarize 18 cyclic peptides approved for clinical use in the past two decades to provide a better understanding of cyclic peptide development and to inspire new perspectives. The purpose of the present review is to promote efforts to resolve the challenges in the development of cyclic peptide drugs that are more effective.

Fig. 1. The chemical structures of cyclic peptides from Tables 1 and 2 that target (a) intracellular proteins and (b) extracellular proteins.

Fig. 2. The chemical structures of cyclic peptide antimicrobial agents from Table 3.