CB-839

Cell lines

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

Preparation method

For viability assays, all cell lines were treated with Telaglenastat at the indicated concentrations for 72 hours in duplicate wells and analyzed for antiproliferative effects using Cell Titer Glo.

Reacting condition

1μM, 72 hours

Applications

Telaglenastat treatment showed a potent effect on the proliferation of HCC1806 and MDA-MB-231 cells with the IC₅₀ of 20–55nM. Telaglenastat (1μM) 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 1μM Telaglenastat for 72 hours. 

Animal models

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

Dosage form

Oral administration; 200mg/kg; twice daily; 28 days

Application

In primary patient-derived TNBC mouse model, oral dosing of single agent Telaglenastat (200mg/kg twice daily) suppressed tumor growth. In the mouse JIMT-1 xenograft model, oral dosing of Telaglenastat alone (200mg/kg twice daily) resulted in 54% tumor growth inhibition (TGI). Combination of Telaglenastat (200mg/kg, p.o.) with paclitaxel (10mg/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.

References:
[1]. Gross M I, Demo S D, Dennison J B, et al. Antitumor activity of the glutaminase inhibitor CB-839 in triple-negative breast cancer[J]. Molecular cancer therapeutics, 2014, 13(4): 890-901.