GNF-5837
作者：齐岳
发布时间：2023-08-28
09:02:37
点击数：
产品名称：GNF-5837
产品描述：
| 产品描述 | GNF-5837 is a specific, and orally bioavailable pan-TRK inhibitor for TrkA/TrkB (IC50: 8/12 nM). |
| 靶点活性 | TrkA:8 nM, TrkB:12 nM |
| 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] |
| 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. |
| 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) |
| 别名 | GNF 5837 |
| 分子量 | 535.503 |
| 分子式 | C28H21F4N5O2 |
| CAS No. | 1033769-28-6 |
存储
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
Ethanol: 5.4 mg/mL (10 mM)
DMSO: 53.6 mg/mL (100 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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西安齐岳生物科技有限公司是集化学科研和定制与一体的高科技化学公司。业务范围包括化学试剂和产品的研发、生产、销售等。涉及产品为通用试剂的分销、非通用试剂的定制与研发，涵盖生物科技、化学品、中间体和化工材料等领域。
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