GNF-2

Catalog No.S2899

For research use only.

GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells.

GNF-2 Chemical Structure

CAS No. 778270-11-4

Selleck's GNF-2 has been cited by 7 Publications

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Biological Activity

Description GNF-2 is a highly selective non-ATP competitive inhibitor of Bcr-Abl, shows no activity to Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells.
Targets
Bcr-Abl (SUP-B15 cell line) [1] Bcr-Abl (K562 cell line) [1]
268 nM 273 nM
In vitro

GNF-2 causes a dose-dependent growth inhibition of the Bcr-abl–positive cell lines with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). GNF-2 inhibits the growth of Ba/F3.p210E255V and Ba/F3.p185Y253H cells with IC50 values of 268 nM and 194 nM respectively. GNF-2 (1 μM) induces apoptosis of Ba/F3.p210 cells as well as Ba/F3.p210E255V cells. GNF-2 inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with IC50 of 267 nM. GNF-2 (1 μM) induces a significant decrease in the levels of phospho-Stat5 in Ba/F3.p210 cells. GNF-2 binds to the myristic binding pocket of Bcr-abl. [1] GNF-2 inhibits the kinase activity of non-myristoylated c-Abl more potently than that of myristoylated c-Abl by binding to the myristate-binding pocket in the C-lobe of the kinase domain. GNF-2 (10 μM) requires BCR and/or the c-Abl SH3 and/or SH2 domains to inhibit BCR-Abl-dependent cell proliferation. GNF-2, but not a methylated GNF-2 analog, binds c-Abl in cellular extracts derived from 3T3 fibroblasts. GNF-2 (10 μM), in a dose-dependent manner, clearly inhibits tyrosine phosphorylation of CrkII. GNF-2 inhibits the phosphorylation of CrkII in c-AblG2A-expressing cells with IC50 of 0.051 μM. [2] GNF-2 binds in an extended conformation in the myristate pocket with the CF3-group buried at the same depth as the final two carbons of the myristate ligand. GNF-2 (10 µM) combined with imatinib (1 µM) reduces the number of resistant clones to 1 µM imatinib by at least 90%. [3] GNF-2 inhibits the auto-phosphorylation and proliferation of BafF3 cells expressing p210Bcr–Abl and p210Bcr–Abl mutants. GNF-2 (8 nM) in combination with GNF-5 (20 nM) results in additive effects with respect to inhibition of the Abl64–515 kinase activity. [4]

Protocol (from reference)

Kinase Assay:[2]
  • Binding assay:

    Recombinant proteins (100 nM for each construct) or immunoprecipitated proteins are diluted in kinase buffer (20 mM HEPES (pH 7.4), 50 mM KCl, 0.1% CHAPS, 30 mM MgCl2, 2 mM MnCl2, 1 mM DTT, and 1% glycerol). Aliquots of the diluted proteins are preincubated with either DMSO or compounds for 30 min at room temperature and then added to K-LISA PTK EAY reaction plates. The kinase reaction is initiated by adding 0.1 mM ATP and is allowed to proceed for 30 min at room temperature. The phosphorylation of GST-Abltide is monitored by SDS-PAGE and phosphorimaging analysis or autoradiography.

Cell Research:[1]
  • Cell lines: Ba/F3.p210, Ba/F3.p210E255V and Ba/F3.p185Y253H cells
  • Concentrations: ~10 μM
  • Incubation Time: 48 hours
  • Method: Cells (0.3-0.6 × 106 per mL) are plated in duplicate or triplicate in 96-well plates containing increasing GNF-2 concentrations (5 nM–10 μM). After incubation at 37 ℃ in 5% CO2 for 48 hours, the effect of GNF-2 on cell viability is determined by the MTT colorimetric dye reduction method. Inhibition of cell proliferation is calculated as a percentage of growth of DMSO-treated cells, and IC50 values are determined with Microsoft Excel XLfit3.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 374.32
Formula

C18H13F3N4O2

CAS No. 778270-11-4
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC(=CC(=C1)C(=O)N)C2=CC(=NC=N2)NC3=CC=C(C=C3)OC(F)(F)F

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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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