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GNF-5837

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Chemical Structure| 1033769-28-6 同义名 : -
CAS号 : 1033769-28-6
货号 : A638163
分子式 : C28H21F4N5O2
纯度 : 99%+
分子量 : 535.492
MDL号 : MFCD24386809
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 30 mg/mL(56.02 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The tropomyosin receptor kinase (TRK) family includes three members of highly homologous receptor tyrosine kinases, TRKA, TRKB, and TRKC that specifically bind to neurotrophins. The binding of neutrophins to the extracellular domains of TRKs causes the kinases to autophosphorylate at several intracellular tyrosine sites and trigger downstream signals involving RAS/ERK, PI3K/AKT, and PLC-γ1 transduction pathways. GNF-5837 is a selective inhibitor of TRKs with IC50s of 8nM and 12nM for TRKA and TRKB, respectively[3]. In proliferation assays utilizing TRK dependent Ba/F3 cells, the inhibitory IC50s of GNF-5837 against cells containing the fusion proteins Tel-TRKA, Tel-TRKB and Tel-TRKC were 11nM, 9nM and 7nM, respectivelyv. In GOT1 cell lines, 2h treatment of GNF-5837 at the concentration of 10nM blocked TRKA activation upon NGF stimulation. The IC50 of GNF-5837 on GOT1 cell proliferation after 144h of incubation was ～660nM. At the concentrations of 5nM, 50nM and 500nM, 24h treatment of GNF-5837 caused downregulation of PI3K-Akt-mTOR signaling and Ras-Raf-MEK-ERK signaling[4]. In xenografts of RIE cells expressing both TRKA and NGF, GNF-5837 was orally administrated daily for 10 days. 72% and 100% tumor regression was observed at the doses of 50mg/kg and 100mg/kg, respectively, while at 25 mg/kg, only partial tumor growth inhibition was achieved[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
BA/F3 cells Proliferation assay Antiproliferative activity against mouse BA/F3 cells expressing Tel-TRKC, IC50=7 nM 24900443
Mo7e cells Function assay Inhibition of c-Kit in human Mo7e cells, IC50=1 μM 24900443
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.87mL

0.37mL

0.19mL

9.34mL

1.87mL

0.93mL

18.67mL

3.73mL

1.87mL
参考文献

[1]Shargh VH, Hondermarck H, et al. Albumin hybrid nanoparticles loaded with tyrosine kinase A inhibitor GNF-5837 for targeted inhibition of breast cancer cell growth and invasion. Int J Pharm. 2016 Dec 30;515(1-2):527-534.

[2]Albaugh P, Fan Y, et al. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med Chem Lett. 2012 Jan 1;3(2):140-5.

[3]Albaugh P, Fan Y, Mi Y, Sun F, Adrian F, Li N, Jia Y, Sarkisova Y, Kreusch A, Hood T, Lu M, Liu G, Huang S, Liu Z, Loren J, Tuntland T, Karanewsky DS, Seidel HM, Molteni V. Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models. ACS Med Chem Lett. 2012 Jan 1;3(2):140-5.

[4]Aristizabal Prada ET, Heinzle V, Knösel T, Nölting S, Spöttl G, Maurer J, Spitzweg C, Angele M, Schmidt N, Beuschlein F, Stalla GK, Blaser R, Kuhn KA, Auernhammer CJ. Tropomyosin receptor kinase: a novel target in screened neuroendocrine tumors. Endocr Relat Cancer. 2018 May;25(5):547-560.