Glutamine can serve as an essential energy source and foundations for a lot of tumor cells. The initial step in glutamine utilization is its conversion to glutamate through the mitochondrial enzyme glutaminase. CB-839 is really a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KGA and GAC). CB-839 had antiproliferative activity inside a triple-negative cancer of the breast (TNBC) cell line, HCC-1806, which was connected having a marked reduction in glutamine consumption, glutamate production, oxygen consumption, and also the steady-condition amounts of glutathione and many tricarboxylic acidity cycle intermediates. In comparison, no antiproliferative activity was noticed in an oestrogen receptor-positive cell line, T47D, and just modest effects on glutamine consumption and downstream metabolites were observed. Across a panel of cancer of the breast cell lines, GAC protein expression and glutaminase activity were elevated in nearly all TNBC cell lines in accordance with receptor positive cells. In addition, the TNBC subtype displayed the finest sensitivity to CB-839 treatment which sensitivity was correlated with (i) reliance on extracellular glutamine for growth, (ii) intracellular glutamate and glutamine levels, and (iii) GAC (although not KGA) expression, a possible biomarker for sensitivity. CB-839 displayed significant antitumor activity in 2 xenograft models: like a single agent inside a patient-derived TNBC model as well as in a basal like HER2( ) cell line model, JIMT-1, both like a single agent and in conjunction with paclitaxel. Together, these data give a strong rationale for that clinical analysis of CB-839 like a targeted therapeutic in patients with TNBC along with other glutamine-dependent tumors.