Telaglenastat hydrochloride

Telaglenastat (CB-839) hydrochloride is a first-in-class, selective, reversible and orally active glutaminase 1 (GLS1) inhibitor. Telaglenastat hydrochloride selectively inhibits GLS1 splice variants KGA (kidney-type glutaminase) and GAC (glutaminase C) compared to GLS2. The IC50s are 23 nM and 28 nM for endogenous glutaminase in mouse kidney and brain, respectively. Telaglenastat hydrochloride inudces autophagy and has antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Telaglenastat (CB-839) (0.1-1000 nM; 72 hours) has antiproliferative activity in HCC1806 and MDA-MB-231 cells with IC50s of 49 nM and 26 nM, respectively[1]. Telaglenastat (CB-839) (1 μM; 72 hours) activates caspase 3/7 and induces apoptosis in MDA-MB-231 and HCC1806 cells[1]. Cell Proliferation Assay[1] Cell Line: HCC1806, MDA-MB-231 cells Concentration: 0.1, 1, 10, 100, 1000 nM Incubation Time: 72 hours Result: Has a potent effect on the proliferation of the two TNBC cell lines (IC50 of 49 nM and 26 nM for HCC1806 and MDA-MB-231 cells). Apoptosis Analysis[1] Cell Line: MDA-MB-231, HCC1806 cells Concentration: 1 μM Incubation Time: 72 hours Result: Caspase 3/7 activation.

Telaglenastat (CB-839) (200 mg/kg; p.o.; twice daily for 28 days) has antitumor activity in xenograft models of TNBC[1]. Animal Model: Female nu/nu mice with age 4–6 weeks (TNBC patient-derived xenograft model)[1] Dosage: 200 mg/kg Administration: Oral administration; twice daily for 28 days Result: Suppressed tumor growth by 61% relative to vehicle control at the end of study.

[1]. Gross MI, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer. Mol Cancer Ther. 2014 Apr;13(4):890-901.

[2]. Biancur DE, et al. Compensatory metabolic networks in pancreatic cancers upon perturbation of glutaminemetabolism. Nat Commun. 2017 Jul 3;8:15965.

[3]. Zhou WJ, et al. Estrogen inhibits autophagy and promotes growth of endometrial cancer by promoting glutamine metabolism. Cell Commun Signal. 2019 Aug 20;17(1):99.