Cell lines

TNBC cell lines HCC1806 and MDA-MB-231, T47D cell line

Preparation method

Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μmol/L, 4 hours

Applications

CB-839 treatment showed a potent effect on the proliferation of HCC1806 and MDA-MB-231 cells with the IC50 of 20–55 nmol/L. CB-839 (1 μmol/L) inhibited the metabolism of glutamine, the rates of glutamine consumption and glutamate production in HCC1806 and T47D cell lines. TNBC cell lines exhibited greater sensitivity as measured by the extent of cell growth or cell loss following treatment with 1 μmol/L CB-839 for 72 hours. CB-839 (1 μmol/L, 72 hours) showed antiproliferative activity on breast cancer cell lines.

Animal models

Scid/Beige mice bearing orthotopically implanted HCC1806 tumors, Patient-derived TNBC and JIMT-1 cell line xenograft models

Dosage form

Oral administration, 200 mg/kg, twice daily

Application

In primary patient-derived TNBC mouse model, oral dosing of single agent CB-839 (200 mg/kg twice daily) suppressed tumor growth. In the mouse JIMT-1 xenograft model, oral dosing of CB-839 alone (200 mg/kg twice daily) resulted in 54% tumor growth inhibition (TGI). Combination of CB-839 (200 mg/kg, p.o.) with paclitaxel (10 mg/kg, p.o.) largely suppressed the regrowth of the tumors resulting in a TGI relative to vehicle control of 100%.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

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

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].

Telaglenastat (CB-839) (200 mg/kg; p.o.; twice daily for 28 days) has antitumor activity in xenograft models of TNBC[1].

References:
[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.