CB 839 is a potent non-competitive glutaminase (GLS1) inhibitor (IC50 = 24 nM for recombinant human GAC). The compound exhibits selectivity for GLS1 over GLS2. CB 839 displays antiproliferative activity in a triple-negative breast cancer cell line (GI50 values are 19 and 55 nM against MDA-MB-231 and HCC1806, respectively); it reduces glutamine consumption and glutamate production rates in HCC1806 cells. CB 839 displays significant antitumor activity as a single agent in a patient-derived TNBC xenografts model. CB 839 inhibits the growth of basal-like HER2 cell line JIMT-1 xenografts in mice, both as a single agent and in combination with Paclitaxel (Cat. No. 1097). CB 839 works with Erlotinib (Cat. No. 7194) to reduce glucose and glutamine uptake, increase energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) non-small cell lung cancer xenografts in vivo. CB 839 is orally bioavailable.
