GlutaminaseC-IN-3 is a potent allosteric inhibitor of glutaminase C (GAC) with an EC50 of 116 nM. It modulates cellular metabolites and elevates reactive oxygen species (ROS) production by inhibiting glutamine metabolism. In A549 xenograft mouse models, GlutaminaseC-IN-3 demonstrates significant antitumor activity. This compound is applicable for research on non-small cell lung cancer (NSCLC).

Glutaminase C:116 nM (EC50)

Glutaminase C-IN-3 (compound 16) exhibits potent antiproliferative activity in A549 cells with an IC50 of 2.45 nM, while selectively affecting normal cells (BEAS-2B) with an IC50 of 1.12 µM. At concentrations of 30-300 nM for 16 hours, it significantly disrupts glutamine metabolism in A549 cells, leading to a concentration-dependent decrease in the glutamate/glutamine ratio. Furthermore, Glutaminase C-IN-3 (300 nM-1 µM, 16 hours) induces a dose-dependent increase in ROS levels in A549 cells, indicating enhanced ROS generation and loss of redox homeostasis. The compound also demonstrates high stability in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) at 5 μM for 1 hour， and shows moderate metabolic stability in rat liver microsomes at 5 μM for 0.25-2 hours.

Compound Glutaminase C-IN-3 (compound 16), administered intraperitoneally at doses of 10 and 30 mg/kg once daily for 22 consecutive days, demonstrates antitumor efficacy with good safety in the A549 xenograft mouse model.