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GNF-7 Bcr-Abl inhibitor

Cat.No.S8140

GNF-7 is a potent type-II kinase Bcr-Abl inhibitor with IC50 of <5 nM, 61 nM, 122 nM, 136 nM, and 133 nM for M351T, T315I, E255 V, G250E, and c-Abl, respectively.
GNF-7 Bcr-Abl inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 547.53

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Quality Control

Batch: Purity: 99.82%
99.82

Solubility

In vitro
Batch:

DMSO : 20 mg/mL (36.52 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : 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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Chemical Information, Storage & Stability

Molecular Weight 547.53 Formula

C28H24F3N7O2

Storage (From the date of receipt)
CAS No. 839706-07-9 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(F)(F)F)N3CC4=CN=C(N=C4N(C3=O)C)NC5=CN=C(C=C5)C

Mechanism of Action

Targets/IC50/Ki
M351T
<5 nM
T315I
61 nM
E255V
122 nM
c-Abl
133 nM
G250E
136 nM
In vitro
GNF-7 shows potent antiproliferative activity against wild-type and mutant Bcr-Abl Ba/F3 cells with IC50 less than 11 nM. In human colon cancer cells (Colo205 and SW620), this compound also displays excellent growth inhibitory activity with IC50 of 5 nM and 1 nM, respectively. It potently and selectively inhibits NRAS-dependent acute myelogenous leukemia and acute lymphoblastic leukemia cells through combined inhibition of ACK1/AKT and GCK.
In vivo
GNF-7 exhibits excellent pharmacokinetic parameters in mice. In a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line, this compound (10 mg/kg, p.o.) effectively inhibits tumor growth. In NSG mice bearing human mutant NRAS-expressing MOLT-3-luc+ tumors, this compound (15 mg/kg, p.o.) significantly decreases disease burden, prolongs overall survival, and causes strong suppression of phospho-AKT and phospho-RPS6.
References

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