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Method to identify specific inhibitors of IMP dehydrogenase

United States Patent

November 28, 2000
View the Complete Patent at the US Patent & Trademark Office
This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.
Collart; Frank R. (Bolingbrook, IL), Huberman; Eliezer (LaGrange, IL)
The University of Chicago (Chicago, IL)
08/ 997,758
December 24, 1997
The U.S. government may have rights in the present invention based an DOE grant No. KP114,63000/011833 between Argonne National Laboratory and the U.S., Department of Energy.