CB-839

CB-839 is an orally bioavailable noncompetitive inhibitor of the glutaminase 1 (GLS1) splice variants, kidney-type (KGA) and glutaminase C (GAC), which convert glutamine into glutamate.¹ CB-839 inhibits human recombinant GAC with IC₅₀ values of less than 50 nM, varying based on the length of preincubation. It inhibits GLS1 activity in tissue homogenates (IC₅₀s = 28 and 23 nM, respectively for brain and kidney), but it does not inhibit GLS2 (IC₅₀ > 1,000 nM for liver). It possesses antiproliferative activity against the triple-negative breast cancer (TNBC) cell lines HCC1806 and MDA-MB-231 (IC₅₀s = 49 and 26 nM, respectively) but not against estrogen receptor-positive T47D cells (IC₅₀ > 1,000 nM). In a patient-derived TNBC mouse xenograft model, CB-839 (200 mg/kg, p.o.) inhibits tumor growth by 61% relative to vehicle control. It also possesses antiproliferative properties in vitro against acute myeloid leukemia (AML) and in synergy with erlotinib (Item No. 10483) in EGFR-driven non-small cell lung cancer (NSCLC) in vitro and in xenografts.^2,3,4

WARNING This product is not for human or veterinary use.

1. Gross, M.I., Demo, S.D., Dennison, J.B., et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol. Cancer Ther. 13(4), 890-901 (2014).

2. Jacque, N., Ronchetti, A.M., Larrue, C., et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 126(11), 1346-1356 (2015).

3. Matre, P., Velez, J., Jacamo, R., et al. Inhibiting glutaminase in acute myeloid leukemia: Metabolic dependency of selected AML subtypes. Oncotarget 7(48), 79722-79735 (2016).

4. Momcilovic, M., Bailey, S.T., Lee, J.T., et al. Targeted inhibition of EGFR and glutaminase induces metabolic crisis in EGFR mutant lung cancer. Cancer 18(3), 601-610 (2017).