Home Protein Tyrosine Kinase Trk receptor inhibitor GNF-5837

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GNF-5837 Trk receptor inhibitor

Cat.No.S7519

GNF-5837 is a selective, and orally bioavailable pan-TRK inhibitor for TrkA, and TrkB with IC50 of 8 nM, and 12 nM, respectively.
GNF-5837 Trk receptor inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 535.49

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Quality Control

Batch: Purity: 99.97%
99.97

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BA/F3 cells Proliferation assay Antiproliferative activity against mouse BA/F3 cells expressing Tel-TRKC, IC50=7 nM
Mo7e cells Function assay Inhibition of c-Kit in human Mo7e cells, IC50=1 μM
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Solubility

In vitro
Batch:

DMSO : 100 mg/mL (186.74 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 9 mg/mL

Water : Insoluble

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In vivo
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 535.49 Formula

C28H21F4N5O2

 Storage (From the date of receipt)
CAS No. 1033769-28-6 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=C(C=C(C=C1)NC(=O)NC2=C(C=CC(=C2)C(F)(F)F)F)NC3=CC4=C(C=C3)C(=CC5=CC=CN5)C(=O)N4

Mechanism of Action

Targets/IC50/Ki
TrkC
(cellular Ba/F3 assays)
7 nM
TrkA
(Cell-free assay)
8 nM
TrkB
(Cell-free assay)
12 nM
In vitro
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.
Kinase Assay
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 (50mM HEPES pH 7.1, 10mM 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 0.2mM 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. This compound is 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. This chemical is 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.
In vivo
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, this compound (100 mg/kg/d p.o.) significantly inhibits tumor growth.
References

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