Telaglenastat (CB-839) hydrochloride is a first-in-class, reversible, and orally active inhibitor of glutaminase 1 (GLS1). It selectively inhibits the splice variants of GLS1, specifically KGA (kidney-type glutaminase) and GAC (glutaminase C), as compared to GLS2. Telaglenastat hydrochloride has an IC50 of 23 nM for endogenous glutaminase in mouse kidney and 28 nM in the brain. In addition, it induces autophagy and exhibits antitumor activity.

Telaglenastat (CB-839), administered at concentrations ranging from 0.1 to 1000 nM for a period of 72 hours, exhibits significant antiproliferative effects on HCC1806 and MDA-MB-231 cell lines, with IC50 values of 49 nM and 26 nM, respectively. Furthermore, at a concentration of 1 μM over the same duration, Telaglenastat activates caspase 3/7 and triggers apoptosis in these cell lines. The findings from the Cell Proliferation Assay and Apoptosis Analysis highlight Telaglenastat's capability to effectively inhibit cell growth and induce apoptosis in TNBC (triple-negative breast cancer) cells, marking its potential in cancer treatment strategies.

Telaglenastat (CB-839) demonstrated antitumor activity in TNBC xenograft models, achieving a 61% suppression of tumor growth relative to vehicle control after twice-daily oral administration (200 mg/kg) for 28 days in female nu/nu mice aged 4-6 weeks. The mice were part of a TNBC patient-derived xenograft model[1].