Current drugs address only ca. 30% of the estimated 3000 disease-relevant targets. Many of these untapped therapeutic applications are intracellular protein-protein interactions (PPIs). The two common classes of drugs, small molecules and biologics, are not a universal solution to all drug discovery challenges (Fig. 1).

Biologics, such as therapeutic antibodies, are ideal for complex and extended targets, but are too large and polar to cross the human cell membrane.  They therefore cannot act inside the cell and are not suitable for oral administration.

Traditional small molecule drugs can access intracellular targets but their limited surface area means they are not suitable for extended binding sites, such as feature in protein-protein interactions. They can only address about 10% of all targets.

Specifically blocking certain protein-protein interactions (Fig. 2) can target a diverse array of diseases, including inflammatory and immunological disorders, infectious diseases, cancer, cardiovascular disease, Alzheimer's and epilepsy (Fig. 3).

Macrocycles and constrained peptides can address extended binding sites and have many of the desirable properties of small molecules.  GyreOx's technology creates a new generation of Gyrocycle^TM constrained macrocyclic peptides, which can be designed to be orally available and membrane permeable (Fig. 4).