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Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology.
Atangcho, Lydia; Navaratna, Tejas; Thurber, Greg M.
Afiliação
  • Atangcho L; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Navaratna T; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Thurber GM; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address: gthurber@umich.edu.
Trends Biochem Sci ; 44(3): 241-257, 2019 03.
Article em En | MEDLINE | ID: mdl-30563724
Stabilized peptide therapeutics have the potential to hit currently undruggable targets, dramatically expanding the druggable genome. However, major obstacles to their development include poor intracellular delivery, rapid degradation, low target affinity, and membrane toxicity. With the emergence of multiple stabilization techniques and screening technologies, the high efficacy of various bioactive peptides has been demonstrated in vitro, albeit with limited success in vivo. We discuss here the chemical and pharmacokinetic barriers to achieving in vivo efficacy, analyze the characteristics of FDA-approved peptide drugs, and propose a developmental tool that considers the molecular properties of stabilized peptides in a comprehensive and quantitative manner to achieve the necessary rates for in vivo delivery to the target, efficacy, and ultimately clinical translation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Peptídeos Cíclicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Peptídeos / Peptídeos Cíclicos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article