Discovery of GuaB Inhibitors for the Treatment of Tuberculosis

Tuberculosis is the leading cause of death from an infectious disease and is caused by Mycobacterium tuberculosis (MTB). Inosine-5′-monophosphate dehydrogenase (GuaB) is an enzyme that performs the rate-limiting step in the de novo biosynthesis of guanine, which is critical for growth of bacteria, including MTB.

The development of a novel antibiotic that inhibits GuaB could potentially combine with existing therapies and contribute to effective therapeutic regimens for the treatment of tuberculosis. WuXi AppTec recently contributed to a study on the discovery of structurally distinct small molecule GuaB inhibitors that are potent against MTB and have desirable safety and ADME profiles.