This report discusses technologies and strategies that enable the discovery of drugs targeting protein-protein interactions (PPIs), covering both small-molecule and synthetic peptidic modulators. The report provides case studies of specific target classes and draws lessons from both the successes achieved and the remaining challenges.
Features and benefits
- Understand why the discovery of PPI modulators has been difficult, and why it is crucial for pharmaceutical companies to overcome these hurdles now.
- Gain insight into the most effective strategies and technologies for discovering PPI modulators.
- Identify companies and academic laboratories that are leaders in the PPI modulator field.
- Identify and evaluate ongoing programs seeking to discover and develop drugs tageting PPIs.
- Understand the limitations of challenges remaining in the field, and thereby identify opportunities for future progress.
Despite the difficulty of the PPI modulator field, one direct PPI agonist –eltrombopag (Ligand/GSK’s Promacta/Revolade) – and two allosteric PPI antagonists – maraviroc (Pfizer’s Selzentry/Celsentri) and plerixafor (Genzyme’s Mozobil) – have reached the market. Several other compounds are in the clinic.
The discovery of currently marketed and clinical-stage compounds was made possible by a set of tools including X-ray diffraction, alanine scanning mutagenesis, fragment-based drug discovery, and conventional medicinal chemistry. Central to this research has been the determination of “hot spots” in protein-protein interfaces
Recently, companies such as Forma, Ensemble, and Aileron, as well as academic laboratories, have been developing second-generation technologies for the discovery of PPI modulators. These technologies are designed to provide a more accelerated and systematic approach to PPI drug discovery and development.
Your key questions answered
- Why has the discovery and development of PPI modulator drugs been found so difficult historically?
- What is to be gained by investing in the discovery of drugs acting at such challenging targets?
- Who have been in the pioneers in the PPI field, and what strategies have they employed to turn PPIs into viable targets?
- Which companies have developed clinical-stage and marketed drugs that modulate protein-protein interactions?
- What second-generation technologies are being developed to accelerate progress in the PPI drug field and where is the field heading?