Peptides as drugs
Peptides and proteins have the size and functionality to effectively modulate intracellular protein–protein interactions, but they often do not permeate cells and, therefore, are used to modulate extracellular targets such as receptors (1, 2). According to a recent analysis of the peptide drug pipeline by the Peptide Therapeutics Foundation (3), the majority of peptide candidates target extracellular molecules with less than 10% binding to intracellular targets. The most common extracellular targets were G-protein coupled receptors (GPCR), which include nearly 1000 transmembrane proteins that activate cellular response. During 2000–2008, 60% of peptides entering clinical development targeted GPCRs and most had agonist activity (3).Although making up only a small portion of total drug candidates, the number of peptide drugs entering clinical development has increased during the past several decades. The Peptide Therapeutics Foundation analysis, which excluded insulins, found that the average number of new peptide candidates entering clinical development in the 1970s was 1.2 per year, rising to 4.6 per year in the 1980s, 9.7 per year in the 1990s and 16.8 per year through 2000–2008 (3). During 2000–2008, peptides entering clinical study were most frequently treatments for cancer and metabolic disorders (including diabetes and obesity), respectively, representing 18% and 17% of peptide drug development. Decreases were observed for peptides studied as therapies for treating allergies, immunological disorders and cardiovascular diseases.
On a commercial level, several peptide-based therapeutics have reached blockbuster status, defined as having sales of $1 billion or more, or near blockbuster status (3). These drugs, using 2011 global sales figures from company annual financial reports, include: