| 名称 | GNF-5837 |
| 描述 | GNF-5837 is a specific, and orally bioavailable pan-TRK inhibitor for TrkA/TrkB (IC50: 8/12 nM). |
| 细胞实验 | Compounds are tested for their ability to inhibit the proliferation of wt Ba/F3 cells and Ba/F3 cells transformed with constitutively expressed luciferase reporter and BCR-ABL or Tel-KDR or other Tel fusion kinases. Parental Ba/F3 cells are maintained in media containing recombinant mouse IL3 and the kinase transformed Ba/F3 cells are maintained in media without IL-3. 7.5 nL of compounds are spotted to each well of 1536-well assay plates by Liquid handling System Echo 555 (Labcyte). 700 cells are then plated into each well of the assay plates in 7 μL culture media per well and compounds are tested at 0.17 nM to 10 uM in 3-fold serial dilutions. The cells were then incubated for 48 hours at 37 °C. 3 μL of Bright-Glo® is added to each well and the plates are read using ViewLux. (Only for Reference) |
| 激酶实验 | Inhibition of biochemical TrkA,TrkB and TrkC: TrkA and TrkC biochemical assays are carried out by HTRF method.The reaction mixtures contains 1 μM peptide substrate,1 μM ATP,and either 1.8 nM TrkA or 34 nM TrkC in the reaction buffer (50 mM HEPES pH 7.1,10 mM MgCl2,2 mM MnCl2,0.01% BSA,2.5 mM DTT and 0.1 mM Na3VO4) at a final volume of 10 μL.All reactions are carried out at room temperature in white ProxiPlate? 384-well Plus plates and are quenched with 5 μL of 0.2 mM EDTA at 60 min.Five μL of the detection reagents (2.5 ng PT66K and 0.05 μg SAXL per well) are added,the plates are incubated at room temperature for 1 h and then read in EnVision reader.Compounds are diluted into assay mixture (final DMSO 0.5%),and IC50 values are determined by 12-point (from 50 to 0.000282 μΜ) inhibition curves in duplicate under the assay conditions.TrkB biochemical assay is carried out by caliper microfluidic method.The reaction mixtures contained 1 μM peptide substrate,10 μM ATP,and 2 nM TrkB in a reaction buffer containing 100 mM HEPES,pH 7.5,5 mM MgCl2,0.01% Triton X-100,0.1% BSA,1 mM DTT,10 μΜNa3VO4,and 10 μΜBeta-Glycerophosphate.The reactions are carried out at room temperature for 3 hrs,and the products are determined by Caliper EZ-reader.Compounds are diluted into assay mixture (final DMSO 1%),and IC50 values are determined by 12-point (from 50 to 0.000282 μΜ) inhibition curves in duplicate under the assay conditions. |
| 体外活性 | In Ba/F3 cells overexpressing the constitutively active Tel-TRKC fusion, GNF-5837 shows potent anti-Trk activity and potent antiproliferation activity with IC50 of 0.042 μM. [1] |
| 体内活性 | In both male Balb/c mice and Sprague–Dawley rats, GNF-5837 has the low drug clearance, and moderate biovailability. In mice bearing Rie xenografts expressing TrkA and NGF, GNF-5837 (100 mg/kg/d p.o.) significantly inhibits tumor growth. [1] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 5.4 mg/mL (10 mM)
DMSO : 40 mg/mL (74.7 mM)
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| 关键字 | Tropomyosin related kinase receptor | Trk Receptor | inhibit | Inhibitor | GNF-5837 | GNF5837 |
| 相关产品 | Gilteritinib | Nintedanib | Regorafenib monohydrate | Sorafenib | Pexidartinib | Regorafenib | Amitriptyline hydrochloride | Sorafenib tosylate | Lenvatinib mesylate | Imatinib | Pazopanib | Axitinib |
| 相关库 | 表型筛选靶点鉴定库 | 经典已知活性库 | 膜蛋白靶向化合物库 | 激酶抑制剂库 | 酪氨酸激酶分子库 | 抑制剂库 | NO PAINS 化合物库 | 口服活性化合物库 | 已知活性化合物库 | 抗癌化合物库 |
United States
