GNF-5837

Catalog No.S7519 Batch:S751901

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Technical Data

Formula

C28H21F4N5O2
Molecular Weight 535.49 CAS No. 1033769-28-6
Solubility (25°C)* In vitro DMSO 100 mg/mL (186.74 mM)
Ethanol 9 mg/mL (16.8 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 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]
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]

Protocol (from reference)

Kinase Assay:

[1]
  • 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 Assay:

[1]
  • 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.
Animal Study:

[1]
  • Animal Models

    Mice bearing Rie xenografts expressing TrkA and NGF.

  • Dosages

    100 mg/kg/d

  • Administration

    p.o.

Selleck's GNF-5837 has been cited by 6 publications

EGFR-phosphorylated GDH1 harmonizes with RSK2 to drive CREB activation and tumor metastasis in EGFR-activated lung cancer [ Cell Rep, 2022, 41(11):111827] PubMed: 36516759
Nerve growth factor orchestrates NGAL and matrix metalloproteinases activity to promote colorectal cancer metastasis [ Clin Transl Oncol, 2021, 10.1007/s12094-021-02666-x] PubMed: 34255268
Trk inhibitor GNF‑5837 suppresses the tumor growth, survival and migration of renal cell carcinoma [ Oncol Rep, 2019, 42(5):2039-2048] PubMed: 31485624
MAST1 Drives Cisplatin Resistance in Human Cancers by Rewiring cRaf-Independent MEK Activation [ Cancer Cell, 2018, 34(2):315-330] PubMed: 30033091
Expression of brain-derived neurotrophic factor and its receptor TrkB is associated with poor prognosis and a malignant phenotype in small cell lung cancer. [ Lung Cancer, 2018, 120:98-107] PubMed: 29748024
Silibinin exerts antidepressant effects by improving neurogenesis through BDNF/TrkB pathway [ Behav Brain Res, 2018, 348:184-191] PubMed: 29680784

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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