research use only

GNF-2 Bcr-Abl inhibitor

Name: GNF-2
SKU: S2899
Availability: InStock
Rating: 5 (8 reviews)

Cat.No.S2899

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.

Chemical Structure

Molecular Weight: 374.32

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.34%

99.34

Related Targets	EGFR VEGFR JAK PDGFR FGFR Src FLT3 HER2 HIF BTK ALK Syk FAK VDA
Related Products	Degrasyn (WP1130) Bafetinib GNF-5 Rebastinib (DCC-2036) Berbamine Olverembatinib (GZD824) dimesylate PD173955 GNF-7 Radotinib Risvodetinib Olverembatinib DPH CZC-8004 Vodobatinib (K0706) ABL1 Antibody [B18C3] XL228 Flumatinib (HH-GV-678) CrkL Antibody [K7G6] Berbamine dihydrochloride

Chemical Information, Storage & Stability

Molecular Weight	374.32	Formula	C₁₈H₁₃F₃N₄O₂	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	778270-11-4	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1=CC(=CC(=C1)C(=O)N)C2=CC(=NC=N2)NC3=CC=C(C=C3)OC(F)(F)F

Solubility

In vitro
Batch:

DMSO : 74 mg/mL (197.69 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.7mg/ml (9.88mM)	Taking the 1 mL working solution as an example, add 50 μL of 74 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	1.27mg/ml (3.39mM)	Taking the 1 mL working solution as an example, add 50 μL of 25.4 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	Bcr-Abl (SUP-B15 cell line) ^[1] 268 nM Bcr-Abl (K562 cell line) ^[1] 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). This compound inhibits the growth of Ba/F3.p210^E255V and Ba/F3.p185^Y253H cells with IC50 values of 268 nM and 194 nM respectively. This chemical (1 μM) induces apoptosis of Ba/F3.p210 cells as well as Ba/F3.p210^E255V cells. It inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with IC50 of 267 nM. This compound (1 μM) induces a significant decrease in the levels of phospho-Stat5 in Ba/F3.p210 cells. It binds to the myristic binding pocket of Bcr-abl. ^[1] This inhibitor 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. This agent (10 μM) requires BCR and/or the c-Abl SH3 and/or SH2 domains to inhibit BCR-Abl-dependent cell proliferation. It, but not a methylated GNF-2 analog, binds c-Abl in cellular extracts derived from 3T3 fibroblasts. This compound (10 μM), in a dose-dependent manner, clearly inhibits tyrosine phosphorylation of CrkII. It inhibits the phosphorylation of CrkII in c-AblG2A-expressing cells with IC50 of 0.051 μM. ^[2] This chemical 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. This compound (10 µM) combined with imatinib (1 µM) reduces the number of resistant clones to 1 µM imatinib by at least 90%. ^[3] It inhibits the auto-phosphorylation and proliferation of BafF3 cells expressing p210Bcr–Abl and p210Bcr–Abl mutants. This agent (8 nM) in combination with GNF-5 (20 nM) results in additive effects with respect to inhibition of the Abl64–515 kinase activity. ^[4]
Kinase Assay	Binding assay
Kinase 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 this compound 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.
References	[1] https://pubmed.ncbi.nlm.nih.gov/16415863/ [2] https://pubmed.ncbi.nlm.nih.gov/19679652/ [3] https://pubmed.ncbi.nlm.nih.gov/20072125/ [4] https://pubmed.ncbi.nlm.nih.gov/20152788/

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):