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GNF-5 Bcr-Abl inhibitor

Cat.No.S7526

GNF-5 is a selective and allosteric Bcr-Abl inhibitor with IC50 of 220 nM.
GNF-5 Bcr-Abl inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 418.37

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Chemical Information, Storage & Stability

Molecular Weight 418.37 Formula

C20H17F3N4O3

 Storage (From the date of receipt)
CAS No. 778277-15-9 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles C1=CC(=CC(=C1)C(=O)NCCO)C2=CC(=NC=N2)NC3=CC=C(C=C3)OC(F)(F)F

Solubility

In vitro
Batch:

DMSO : 84 mg/mL (200.77 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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Mass Concentration Volume Molecular Weight

In vivo
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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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Mechanism of Action

Targets/IC50/Ki
Bcr-Abl [1]
220 nM
In vitro

GNF-5, when used in combination, suppresses the emergence of resistance mutations in vitro, and displays additive inhibitory activity in biochemical and cellular assays against Bcr-Abl T315I mutant. [1] This compound shows potent antiproliferative activity with EC50 of 430 nM and 580 nM against wt-Bcr-Abl and E255K mutant Bcr-Abl transformed cells, respectively. [2]
Kinase Assay
Kinetic characterization of Abl inhibition
The ATP/NADH-coupled assay system in a 96-well format is used to determine the initial velocity of Abl tyrosine kinase catalyzed peptide phosphorylation. The reaction mixture contained 20 mM Tris-HCl, (pH 8.0), 50 mM NaCl, 10 mM MgCl2, 2 mM PEP [2-(Phosphonooxy)- 2-propenoic acid) and 20 μg Abl peptide substrate (EAIYAAPFAKKK), fixed or varied (to determine inhibitor kinetic parameters) concentration of this compound applied, 1/50 of the final reaction mixture volume of PK/LDH enzyme (pyruvate kinase/lactic dehydrogenase enzymes from rabbit muscle), 160 μM NADH, 0.16 μM Abl, and ATP added last to start the reaction. Absorbance data are collected every 20s at 340 nm using a SpectraMax M5 Microplate Reader.
In vivo

GNF-5 (100 mg/kg ) displays efficacy on wild-type and T315I Bcr-Abl dependent proliferation in xenograft and bone marrow transplantation models. Moreover, a combination of this compound (75 mg/kg) results in improved overall survival in a T315I Bcr-Abl BMT model. [1]
References

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