Home Protein Tyrosine Kinase Trk receptor inhibitor GNF-5837 For research use only.

GNF-5837

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 Chemical Structure

GNF-5837 Chemical Structure

CAS No. 1033769-28-6

Purity & Quality Control

GNF-5837 Related Products

Signaling Pathway

Trk receptor Signaling Pathways

Trk receptor Signaling Pathway

Cell Data

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 24900443
Mo7e cells Function assay Inhibition of c-Kit in human Mo7e cells, IC50=1 μM 24900443
Click to View More Cell Line Experimental Data

Biological Activity

Description GNF-5837 is a selective, and orally bioavailable pan-TRK inhibitor for TrkA, and TrkB with IC50 of 8 nM, and 12 nM, respectively.
Targets
TrkC [1]
(cellular Ba/F3 assays)		 TrkA [1]
(Cell-free assay)		 TrkB [1]
(Cell-free assay)
7 nM 8 nM 12 nM
In vitro
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. [1]
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. 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.
Cell Research Cell lines 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
Concentrations ~10 μΜ
Incubation Time 48 hours
Method

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.
In Vivo
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, GNF-5837 (100 mg/kg/d p.o.) significantly inhibits tumor growth. [1]
Animal Research Animal Models Mice bearing Rie xenografts expressing TrkA and NGF.
Dosages 100 mg/kg/d
Administration p.o.

Chemical Information & Solubility

Molecular Weight 535.49 Formula

C28H21F4N5O2
CAS No. 1033769-28-6 SDF Download GNF-5837 SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (186.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 9 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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