CB-839 | Glutaminase inhibitor

CB-839 (14393999-58-2) is a potent (IC₅₀ = 24 nM), selective and orally bioavailable inhibitor of glutaminase (KGA and GAC).¹ CB-839 displayed an antiproliferative effect in the triple-negative breast cancer cell line, HCC-1806, but no activity in the estrogen receptor-positive cell line T47D.  CB-839 was able to cause proliferation arrest and apoptosis in acute myeloid leukemia cells without causing cytotoxicity against normal human CD34(+) progenitors.²  Aspartate-glutamate carrier 1 (AGC1) inhibition can synergize with CB-839 to limit tumor growth.³

References/Citations
1) Gross et al. (2014), Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer; Mol. Cancer Ther.,13 890
2) Jacque et al. (2015), Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition; Blood, 126 1346
3) Alkan et al. (2018) Cytosolic Aspartate Availability Determines Cell Survival When Glutamine is Limiting; Cell Metabolism 28 1