NIH Record - National Institutes of Health

International Scientific Teams Find Potential Approach Against Parasites

Scientific rendering of curled blue ribbons and curled green ribbons joined at center by multicolor pebbles
The cyclic peptide ipglycermide binds to an iPGM enzyme, blocking its activity.

Research teams from NIH and abroad have identified the first inhibitor of an enzyme long thought to be a potential drug target for fighting disease-causing parasites and bacteria. The teams, led by NCATS and University of Tokyo scientists, sorted through more than 1 trillion small protein fragments called cyclic peptides to uncover two that could shut down the enzyme. 

The finding, reported Apr. 3 in Nature Communications, could set the stage for the potential development of new types of antimicrobial drugs.

NCATS’ expertise in early-stage, pre-clinical molecule discovery helped the teams find potential drug candidates that could have implications for millions of people worldwide. 

“The work is an excellent demonstration of how NCATS delivers on its mission to provide improvements in translational processes,” said Dr. Anton Simeonov, scientific director, NCATS Division of Pre-Clinical Innovation. “Scientists have shown that a therapeutic target, previously considered undruggable by pharmaceutical companies, is actually druggable through a non-traditional therapeutic agent.”

The target enzyme, cofactor-independent phosphoglycerate mutase (iPGM), is found in both parasites and bacteria. 

Several types of parasitic roundworms have iPGM, including Brugia malayi and Onchocerca volvulus, which infect roughly 150 million people living mostly in tropical regions. These parasites can cause devastating infectious diseases such as river blindness. 

The enzyme also is found in bacteria, including Staphylococcus aureus, which can cause the hospital-borne infection MRSA (methicillin-resistant Staphylococcus aureus), and Bacillus anthracis, which causes anthrax.

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