Discovery of Pks13 Inhibitors for the Treatment of Tuberculosis through DNA-encoded Chemical Library Screening
Here we report the use of DNA encoded Library (DEL) to identify a novel chemical series of inhibitors of the thioesterase activity of polyketide synthase 13 (Pks13) from Mycobacterium tuberculosis (Mtb). We present three chemically distinct series of inhibitors along with their biochemical and cellular potencies. One of these inhibitors showed a favorable pharmacokinetics profile and efficacy in an acute mouse model of tuberculosis (TB) infection.