Description:
Project ID: D2015-58
Invention Description:
The expanding populations of microbes that have developed resistance to many of the available antibiotics require new drugs which can act through novel mechanisms to thwart this increasing resistance. Our technology provides the basis for development of selective drugs that can function through a novel mechanism of action against this new target.
Novelty:
New set of structures opens an untested direction for the development of inhibitors against this validated drug-target enzyme, showing excellent affinity to the target enzyme and very good selectivity between Gram-negative and Gram-positive bacterial orthologs and other closely related bacterial and fungal enzymes.
Applications: Our identification of effective inhibitors against this target enzyme will provide lead compounds for the development of new biocides with unique modes of action. Achieving selective inhibition of related enzymes from different microorganisms will lead to species-specific biocides that will further delay the development of drug resistance.
Value proposition:
• We have discovered the mechanism by which blockage of the metabolic pathway -- fatal to microorganisms and absent in humans -- can occur.
• Inhibition of this key enzyme will provide the basis for development of selective drugs that can function through a novel mechanism of action against this new target.
• Every inhibitor previously examined showed only modest affinity against these target enzymes. Our approach has resulted in the synthesis of unusual low micromolar inhibitors of the target enzyme, with high selectivity and significantly greater affinity than previously observed.
IP Status: 10,449,168B2