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Trends in peptide drug discovery

Abstract

Since the introduction of insulin almost a century ago, more than 80 peptide drugs have reached the market for a wide range of diseases, including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain. In this Perspective, we summarize key trends in peptide drug discovery and development, covering the early efforts focused on human hormones, elegant medicinal chemistry and rational design strategies, peptide drugs derived from nature, and major breakthroughs in molecular biology and peptide chemistry that continue to advance the field. We emphasize lessons from earlier approaches that are still relevant today as well as emerging strategies such as integrated venomics and peptide-display libraries that create new avenues for peptide drug discovery. We also discuss the pharmaceutical landscape in which peptide drugs could be particularly valuable and analyse the challenges that need to be addressed for them to reach their full potential.

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Fig. 1: Historical timeline of key milestones, developments and drug approvals in the peptide therapeutics field.
Fig. 2: The peptide drug market.
Fig. 3: Selected examples of therapies based on peptide hormones.
Fig. 4: Selected examples of therapies based on natural product peptides.
Fig. 5: Peptide drug discovery strategies.
Fig. 6: Medicinal chemistry strategies for peptide drugs.

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Acknowledgements

The authors thank K. Woolcock for help with editing the manuscript. M.M. is supported by the European Research Council under the European Union’s Horizon 2020 research and innovation programme (714366), by the Australian Research Council (DE150100784 and DP190101667) and by the Vienna Science and Technology Fund (WWTF; LS18-053). P.F.A., G.F.K. and D.J.A. were supported by Program Grant APP1072113 from the Australian National Health & Medical Research Council (NHMRC) and NHMRC Principal Research Fellowships to G.F.K. (APP1136889) and P.F.A. (APP1080593).

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Muttenthaler, M., King, G.F., Adams, D.J. et al. Trends in peptide drug discovery. Nat Rev Drug Discov 20, 309–325 (2021). https://doi.org/10.1038/s41573-020-00135-8

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