Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule
Autor: | Arasu Ganesan, Flavio da Silva Emery, Gabriela B. Santos |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Drug media_common.quotation_subject Molecular Conformation Administration Oral Peptide Pharmacology 01 natural sciences Biochemistry 03 medical and health sciences Pharmacokinetics Oral administration Drug Discovery Humans FÍSICO-QUÍMICA General Pharmacology Toxicology and Pharmaceutics media_common chemistry.chemical_classification 010405 organic chemistry Drug discovery Organic Chemistry Cyclic peptide 0104 chemical sciences 030104 developmental biology chemistry Lipinski's rule of five Molecular Medicine Peptides Peptide drug |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 1860-7179 |
Popis: | The use of peptides in therapy presents several limitations, from physicochemical characteristics to inadequate pharmacokinetic profiles for oral absorption. As peptides are gaining importance in the therapeutic arsenal, there is an increasing need to rationalize the main characteristics of this compound class in the market. Therefore, we performed an extensive analysis of all known peptide drugs and clinical candidates based on their peptide features, physicochemical and structural properties, and correlated these with their administration route and therapeutic classes. Peptide drugs are widely distributed across drug and pharmacological space, covering several therapeutic areas with structural diversity and complexity, distributed between groups of cyclic and linear compounds. Although structural and physicochemical properties are clear within these groups, we counter the consensus that cyclic peptides have better oral availability than linear peptides, as most of the orally administrated peptides have linear structures. This study and review furnishes information that could support peptide drug design, with a new cutoff of known descriptors that go beyond the Rule of Five. |
Databáze: | OpenAIRE |
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