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 |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 20%HP-β-CD/10 mM citrate pH 2.0 Solubility: 10 mg/mL (17.50 mM); Clear solution; Need ultrasonic 2. 请依序添加每种溶剂： 20%SBE-β-CD/10 mM Trisodium citrate adjusted to pH 2.0 with HCL Solubility: 5 mg/mL (8.75 mM); Clear solution; Need ultrasonic and adjust pH to 2 with 1M HCl and heat to 55℃ 3. 请依序添加每种溶剂： 70%PEG300 30% (20%SBE-β-CDin saline) Solubility: 4 mg/mL (7.00 mM); Suspended solution; Need ultrasonic and warming and heat to 55℃
*以上所有助溶剂都可在本网站选购。 |
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