GNF 5 |
Catalog No.GC15079
One-Click Copy Product Info
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Bcr-Abl inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 778277-15-9
Sample solution is provided at 25 µL, 10mM.
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GNF-5 is an analogue of GNF-2 and a selective non-ATP competitive inhibitor of Bcr-Abl with an IC50 value of 0.1 to >10 µM in various cancer cell lines.
Bcr-Abl is a fusion gene that results from the head-to-tail fusion of the Bcr and Abl genes[1]. Bcr-Abl upregulates production of tyrosine kinase and plays a central role in the pathogenesis of chronic myelogenous leukemia (CML) [1].
GNF-5 has the same chemical structure as its parent molecule (GNF-2) with the exception of N-hydroxyethyl carboxamide at its 4-position and such modification provided GNF-5 a longer half-life from (2.30 hrs)[2]. Similar with GNF-2, GNF-5 allosterically inhibits the proliferation of Bcr-Abl positive cell by binding to the myristate-binding site of Abl and induces cell apoptosis[3]. In steady-state kinetic analyses, GNF-5 was able to inhibit wild type Abl with an IC50 value of 0.22 µM[2]. In addition, GNF-5 also has a similar effectiveness against various imatinib® resistance cell lines: In E255V and T315I mutant Ba/F3 cells, a 12-day incubation of GNF-5 2 was able to inhibit the proliferation of cells with a IC50 value of 0.38 and 5 µM, respectively[2].
In mice injected with wild-type Bcr-Abl and luciferase expressing Ba/F3 cells, continuous injection of GNF-5 for 7 days (50 mg/kg, twice per day) normalized peripheral blood cell counts, as well as spleen size[2]. When treating mice that injected with imatinib® resistance T315I Bcr–Abl-transduced bone marrow, daily injection of GNF-5 (75 mg/ kg, twice per day) significantly extended the survival day of mice from 24 days to 22 days[2].
References:
[1]. Rumpold, H. & Webersinke, G. 2011. Molecular pathogenesis of Philadelphia-positive chronic myeloid leukemia - is it all BCR-ABL? Curr Cancer Drug Targets, 11, 3-19.
[2]. Zhang, J., Adrian, F. J., Jahnke, W., et al. 2010. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature, 463, 501-506.
[3]. Karunakaran, U., Park, S. J., Jun, D. Y., et al. Non-receptor tyrosine kinase inhibitors enhances β-cell survival by suppressing the PKCδ signal transduction pathway in streptozotocin – induced β-cell apoptosis. Cellular Signalling.
| Cell experiment:[1] | |
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Cell lines |
Wild-type or Bcr-Abl transformed Ba/F3 cells |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
0-3 μM |
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Applications |
Inhibition of wild-type Abl was observed for both inhibitors with GNF-5 exhibiting an IC50 value of 0.22 mM, dasatinib using an ATP concentration of 20 mM with an IC50 value of 0.12 mM. The myristate site mutant E505K was inhibited by dasatinib with an IC50 value of 0.02 mM, but not by GNF-5 (IC50>10 mM). |
| Animal experiment:[2] | |
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Animal models |
Abl-lox and SM22cre mice on C57BL/6 background |
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Dosage form |
Animals were intranasally instilled with 10 mg/kg GNF-5 or PBS 1 h before OVA instillation and 5 h after OVA instillation for last three weeks. |
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Applications |
In conditional knockout of Abl mice, the levels of IL-13 and CCL2 in bronchoalveolar lavage fluid treated with ovalbumin has not been affected, but it works after treatment with imatinib and GNF-5 as well as airway resistance and smooth muscle growth in animals. Treatment with imatinib or GNF-5 inhibited the ACh-induced contraction in isolated mouse tracheal rings of OVA-sensitized and challenged mice. Treatment with imatinib or GNF-5 diminished the fluorescent intensity of PCNA in BALB/c mice treated with OVA. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Iacob RE, Zhang J, Gray NS et al. Allosteric interactions between the myristate- and ATP-site of the Abl kinase. PLoS One. 2011 Jan 10;6(1):e15929. [2]. Cleary RA, Wang R, Wang T et al. Role of Abl in airway hyperresponsiveness and airway remodeling. Respir Res. 2013 Oct 11;14:105. |
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| Cas No. | 778277-15-9 | SDF | |
| Chemical Name | N-(2-hydroxyethyl)-3-[6-[4-(trifluoromethoxy)anilino]pyrimidin-4-yl]benzamide | ||
| Canonical SMILES | C1=CC(=CC(=C1)C(=O)NCCO)C2=CC(=NC=N2)NC3=CC=C(C=C3)OC(F)(F)F | ||
| Formula | C20H17F3N4O3 | M.Wt | 418.37 |
| Solubility | ≥ 20.9mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3902 mL | 11.9511 mL | 23.9023 mL |
| 5 mM | 478 μL | 2.3902 mL | 4.7805 mL |
| 10 mM | 239 μL | 1.1951 mL | 2.3902 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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.)
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 saline, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)