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Overcoming Cellular and Systemic Barriers to Design the Next Wave of Peptide Therapeutics

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Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Peptide drugs cover therapeutic space that is complementary to small molecules and protein therapeutics. Although peptide drugs have been in use for over 50 years, recent advances in understanding the additional target space afforded by peptide drugs, as well as technical achievements in peptide synthesis and screening have reinvigorated interest in peptide drugs as an addition to our therapeutic tool chest. Indeed, novel combinatorial strategies enable de novo generation of potent ligands to specific targets capable of inhibiting protein–protein interactions. Conversion of these ligands into drugs is challenging, requiring optimization of membrane permeability and intracellular exposure, and pharmacokinetic properties while maintaining prescribed pharmacological activities. This chapter provides an overview of the diversity of peptide drugs emerging as novel therapeutics, and challenges to achieving cellular and in vivo exposure required to support pharmacological efficacy. Summarizing the challenges from early discovery through to clinical translation, a hierarchal strategy is presented for peptide discovery in which structural diversity in early discovery stages are used to inform opportunities leading to clinical candidates.

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Author information

Authors and Affiliations

  1. Modalities ADME, Lansdale, PA, USA

    Jerome Hochman

  2. Maestro Therapeutics, Southborough, MA, USA

    Tomi Sawyer

  3. Department of PPDM Merck & Co., Inc., Boston, MA, USA

    Ruchia Duggal

Authors
  1. Jerome Hochman
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  2. Tomi Sawyer
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  3. Ruchia Duggal
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Editors and Affiliations

  1. College of Pharmacy, University of Michigan, Ann Arbor, MI, USA

    Gus R. Rosania

  2. Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA

    Greg M. Thurber

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Hochman, J., Sawyer, T., Duggal, R. (2021). Overcoming Cellular and Systemic Barriers to Design the Next Wave of Peptide Therapeutics. In: Rosania, G.R., Thurber, G.M. (eds) Quantitative Analysis of Cellular Drug Transport, Disposition, and Delivery. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1250-7_10

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  • DOI: https://doi.org/10.1007/978-1-0716-1250-7_10

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