GNF-5837 是一种有效的，选择性的，口服生物利用的泛TRK抑制剂，在 Ba/F3 细胞中显示出抗增殖作用 (对Tel-TrkC,Tel-TrkB和Tel-TrkA的IC50值分别为 7 nM，9 nM 和 11 nM)。
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| 生物活性 | GNF-5837 is a potent, selective, and orally bioavailable pan-tropomyosin receptor kinase (TRK)inhibitor which display antiproliferative effects in cellular Ba/F3 assays (IC50values of 7 nM, 9 nM and 11 nM for cells containing the fusion proteinsTel-TrkC,Tel-TrkBandTel-TrkA, respectively)[1]. |
| IC50& Target | TrkB 9 nM (IC50) | TrkC 7 nM (IC50) | TrkA 11 nM (IC50) |
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体外研究
(In Vitro) | GNF-5837 (0.1-500 nM; 72-144 hours; GOT1 cells) treatment decreases cell viability in a time- and dose-dependent manner in GOT1 cells[2].
GNF-5837 (5-500 nM; 24 hours; GOT1 cells) causes downregulation of PI3K-Akt-mTOR signaling, Ras-Raf-MEK-ERK signaling[2].
GNF-5837 (5-500 nM; 72 hours; GOT1 cells) treatment induces G1 cell cycle arrest[2].
GNF-5837 (500 nM; 144 hours; GOT1 cells) treatment increases apoptotic cell death[2].
Cell Viability Assay[2] | Cell Line: | GOT1 cells | | Concentration: | 0.1 nM , 0.5 nM , 1 nM , 5 nM , 10 nM , 50 nM , 100 nM and 500 nM | | Incubation Time: | 72 hours, 96 hours and 144 hours | | Result: | Cell viability assay determined a clear decrease of GOT1 cell viability in a time- and dose- dependent manner. |
Western Blot Analysis[2] | Cell Line: | GOT1 cells | | Concentration: | 5 nM, 50 nM and 500 nM | | Incubation Time: | 24 hours | | Result: | Significant levels of TrkA expression, faint TrkC expression and no TrkB expression. |
Cell Cycle Analysis[2] | Cell Line: | GOT1 cells | | Concentration: | 5 nM, 500 nM | | Incubation Time: | 72 hours | | Result: | Induced G1 cell cycle arrest. |
Apoptosis Analysis[2] | Cell Line: | GOT1 cells | | Concentration: | 500 nM | | Incubation Time: | 144 hours | | Result: | Induced apoptosis. |
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体内研究
(In Vivo) | GNF-5837 (25-100 mg/kg; oral administration; once daily; for 10 days; mice) treatment inhibits tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF[1].
| Animal Model: | Mouse xenograft model[1] | | Dosage: | 25 mg/kg, 50 mg/kg, 100 mg/kg | | Administration: | Oral administration; once daily; for 10 days | | Result: | 72 and 100% tumor regression was observed at 50 and 100 mg/kg, respectively. At 25 mg/kg, only partial tumor growth inhibition was achieved. |
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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 : ≥ 32 mg/mL(59.76 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.8674 mL | 9.3372 mL | 18.6745 mL | | 5 mM | 0.3735 mL | 1.8674 mL | 3.7349 mL | | 10 mM | 0.1867 mL | 0.9337 mL | 1.8674 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： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (4.67 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.67 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (4.67 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (4.67 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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