glutaminase c-in-1

Glutaminase C-IN-1 (Compound 968) is an allosteric inhibitor of Glutaminase C (GLS1).

Telaglenastat (CB-839) hydrochloride is a first-in-class, reversible, and orally active inhibitor of glutaminase 1 (GLS1), selectively inhibiting the splice variants KGA (kidney-type glutaminase) and GAC (glutaminase C), as opposed to GLS2. Telaglenastat hydrochloride has an IC50 of 23 nM for endogenous glutaminase in mouse kidney and 28 nM in the brain, inducing autophagy and exhibiting antitumor activity.

Glutaminase C-IN-2 (compound 11), an allosteric inhibitor of glutaminase C (GAC), shows potent inhibitory activity with an IC50 of 10.64 nM. By disrupting glutamine metabolism, it modulates cellular metabolites and elevates reactive oxygen species (ROS), exerting anticancer effects [1].

Glutaminase C Inhibitor 11 is a potent inhibitor specifically targeting Glutaminase C (GAC), demonstrating significant inhibition of GAC enzyme activity with an EC50 value of 10.64 nM. It effectively diminishes the viability of A549 non-small cell lung cancer (NSCLC) cells, presenting an IC50 of 4.025 nM. Moreover, at concentrations of 0.1 and 1 µM, it substantially impedes colony formation and reduces intracellular glutamate levels in A549 cells. Demonstrating efficacy in vivo, Glutaminase C Inhibitor 11 at a dosage of 100 mg/kg markedly curtails tumor growth in an A549 mouse xenograft model.