Oral Administration of Peptide-Based Drugs: Beyond Lipinski's Rule.
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.
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Cafe s/n, Cidade Universitaria, Ribeirao Preto, SP, Brazil.
Gabriela B
GB
Santos
School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
A
A
Ganesan
School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Cafe s/n, Cidade Universitaria, Ribeirao Preto, SP, Brazil. flavioemery@fcfrp.usp.br.
Flavio S
0000-0002-8652-7123
FS
Emery
D000284:Administration, Oral; D006801:Humans; D008968:Molecular Conformation; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*
D010455:Peptides
drug discovery; drug likeness descriptors; drugs; peptides; physicochemical properties