New strategies are needed to combat serious infectious diseases, especially in the growing population of immunocompromised patients.
Existing drug development initiatives do not target specific patient populations and miss the opportunity to impact their distinct natural histories. Our approach allows the natural history of a disease to guide the development plan of new molecular entities.
Our lead compound, ARV-1502, is a Designer Proline-rich antimicrobial peptide Chaperone protein inhibitor (DPC). ARV-1502 is a short peptide with multiple modes of action including bacterial protein folding inhibition (via DnaK), bacterial protein translation inhibition (70S ribosome) and at higher doses, bacterial cell membrane disruption. These inhibitory activities are augmented when a bacterial cell is stressed, such as concomitant exposure to antibiotics.
ARV-1502 Mechanism of Action
Bacterial functions are dependent on properly folded proteins that are required for cellular machinery. The folding of these proteins requires chaperone proteins to make sure that the folding occurs correctly. One of the central chaperone proteins in bacteria responsible for such folding is DnaK. Improperly folded bacterial proteins make bacterial cells more susceptible to external stressors, as an example, antibiotic exposure. ARV-1502 acts as a DnaK inhibitor disrupting protein folding and increasing susceptibility to antibiotics.