Telaglenastat (CB-839) 是一种首创的,选择性的,可逆性的,口服活性的谷氨酰胺酶 1 (GLS1) 抑制剂。Telaglenastat 抑制GLS1剪接变异体KGA和GAC,比 GLS2 具有更高的选择性。Telaglenastat 对小鼠类肾和脑中的内源性谷氨酰胺酶的IC50值分别为 23 nM 和 28 nM。Telaglenastat 还可诱导细胞自噬 (autophagy),并具有强大的抗肿瘤活性。
生物活性 | Telaglenastat (CB-839) is a first-in-class, selective, reversible and orally activeglutaminase1 (GLS1)inhibitor. Telaglenastat selectively inhibitsGLS1splice variantsKGA (kidney-type glutaminase)andGAC (glutaminase C)compared to GLS2. TheIC50s are 23 nM and 28 nM for endogenousglutaminasein mouse kidney and brain, respectively. Telaglenastat inuducesautophagyand has antitumor activity[1]. |
IC50& Target | IC50: 23 nM (GLS1 in kidney), 28 nM (GLS1 in brain), >1 μM (GLS2 in liver)[1] |
体外研究 (In Vitro) | 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 (IC50of 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. |
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体内研究 (In Vivo) | 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. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : 6.29 mg/mL(11.00 mM;Need ultrasonic) 配制储备液 1 mM | 1.7496 mL | 8.7478 mL | 17.4957 mL | 5 mM | 0.3499 mL | 1.7496 mL | 3.4991 mL | 10 mM | 0.1750 mL | 0.8748 mL | 1.7496 mL |
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