Discovery of IPN60090, a Clinical Stage Selective Glutaminase‑1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties

Inhibition of glutaminase-1 (GLS-1)
hampers the proliferation of
tumor cells reliant on glutamine. Known glutaminase inhibitors have
potential limitations, and in vivo exposures are potentially limited
due to poor physicochemical properties. We initiated a GLS-1 inhibitor
discovery program focused on optimizing physicochemical and pharmacokinetic
properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials.
Compound 27 attains high oral exposures in preclinical
species, with strong in vivo target engagement, and should robustly
inhibit glutaminase in humans.