Novel HPPK (Bacterial Protein) Inhibitors for Use as Antibacterial Agents

Abstract:

Research and development leading to the discovery of novel antibiotics has waned in recent years. At the same time, the emergence and spread of antimicrobial resistance has compounded the global danger to human health from bacterial infections. 

The bacterial protein 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a key enzyme in the folate biosynthetic pathway. This pathway is essential for bacteria and microorganisms but is absent in mammals – making it an attractive target for antibiotics. HPPK is a novel target for antibiotics as none of the antimicrobial agents currently on the market or in later stage development are HPPK inhibitors.

Researchers at the NCI have developed several novel small-molecule inhibitors directed against HPPK for potential use as antimicrobial agents. The compounds described in this invention present strong binding affinity for HPPK with Kd values as low as 50 nM. 

The NCI seeks co-development partners or licensees to further develop these novel small-molecule HPPK inhibitors as broad-spectrum bactericidal agents.

Competitive Advantages:

• HPPK represents a novel target for these first-in-class high-affinity antibacterial compounds
• Lack of the folate biosynthetic pathway in humans suggest anti-infectives targeting this pathway might be well-tolerated

Commercial Applications:

• Potential use as a broad-spectrum or narrow-spectrum antibiotic 
• Potential use in antibacterial consumer products
• Potential use as a biodefense therapeutic
• Potential use for parasitic diseases, such as malaria
• Increases in the worldwide prevalence of persistent and infectious diseases and the promise of new antibiotics to address a broad spectrum of organisms are driving growth of the global market
• Growing populations and increasing healthcare expenditures are key factors driving growth of the global market