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Purity: ≥98%
GNF-2 (GNF 2; GNF2) is a highly potent, selective and allosteric/non-ATP competitive inhibitor of Bcr-Abl with potential anticancer activity. It shows no activity against Flt3-ITD, Tel-PDGFR, TPR-MET and Tel-JAK1 transformed tumor cells. GNF-2 acts by allosterically binding the myristate-binding site of ABL and inhibits the proliferation of BCR-ABL positive cell and induces cell apoptosis. GNF-2 eliminated transplanted-CML-T315I-mutants in vivo and dose dependently sensitized primary cells from CML T315I patients to GNF-2-induced proliferation inhibition and apoptosis
| ln Vitro |
GNF-2 inhibits Bcr-abl-dependent cell proliferation in a specific manner. GNF-2 (0.005-10 μM; 48 hours) does not exhibit any cytotoxic effects at concentrations up to 10 μM on nontransformed cells, but it specifically inhibits the proliferation of Bcr-abl-expressing cells with an IC50 of 138 nM. The Bcr-abl-positive cell lines exhibit a dose-dependent growth inhibition in response to GNF-2 (0.005-10 μM; 48 hours), with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). E255V and Y253H mutant Bcr-abl cell growth is inhibited by GNF-2 (0.005-10 μM; 48 hours) (IC50 values of 268 and 194 nM, respectively)[1]. Bcr-abl-transformed cells undergo apoptosis when exposed to GNF-2 (1–10 μM) for 48 hours[1]. With an IC50 of 267 nM, GNF-2 (0.1–10 μM; 90 minutes) inhibits Bcr-abl's cellular tyrosine phosphorylation in a dose-dependent manner[1].
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| ln Vivo |
In mice, GNF-2 (10 mg/kg; ip for 8 days) prevents bone degradation caused by LPS (5 mg/kg). GNF-2 prevents LPS-induced bone loss and reverses LPS-induced reductions in the BV/TV (bone volume/tissue volume) of mice exposed to LPS[2]. GNF-2 inhibits the increases in N.Oc/B.Pm, Oc.S/BS, and ES/BS that are brought on by LPS[2].
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Ba/F3.p210, Ba/F3.p210E255V and Ba/F3.p185Y253H cells Tested Concentrations: 0.005, 0.01, 0.1, 1, 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited Bcr-abl-transformed cells proliferation. Apoptosis Analysis[1] Cell Types: Ba/F3.p210 and Ba/F3.p210E255V cells Tested Concentrations: 1, 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Increased number of Ba/F3 .p210 cells underwent apoptosis at 1 μM for 48 h. Ba/F3.p210E255V underwent apoptotic death after 48 h incubation in the presence of 1 μM or higher concentration. Western Blot Analysis[1] Cell Types: Ba/F3.p210 and Ba /F3.p210E255V cells Tested Concentrations: 0.1, 1, 10 μM Incubation Duration: 90 minutes Experimental Results: diminished the autophosphorylation levels at a concentration of 1 μM and were barely detectable at 10 μM, whereas the level of total Bcr-abl remained unchanged. Induced a significant decrease in the levels of p-Stat5 (at Y694) at 1 μM in Ba/F3.p210 and Ba/F3.p210E255V cells. |
| Animal Protocol |
Animal/Disease Models: Eightweeks old C57/BL6 black mouse were administered ip injections of LPS (5 mg/kg)[2]
Doses: 10 mg/kg Route of Administration: Ip injections for 8 days; 1 day before and every day after the LPS injection Experimental Results: Prevented inflammatory bone destruction in vivo. |
| References |
[1]. Adrián FJ, et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb;2(2):95-102.
[2]. Kim HJ, et al. The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity. J Leukoc Biol. 2013 Oct 15. |
| Molecular Formula |
C18H13F3N4O2
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| Molecular Weight |
374.32
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| CAS # |
778270-11-4
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| Related CAS # |
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| SMILES |
O=C(C1=CC=CC(C2=CC(NC3=CC=C(OC(F)(F)F)C=C3)=NC=N2)=C1)N
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| InChi Key |
WEVYNIUIFUYDGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H13F3N4O2/c19-18(20,21)27-14-6-4-13(5-7-14)25-16-9-15(23-10-24-16)11-2-1-3-12(8-11)17(22)26/h1-10H,(H2,22,26)(H,23,24,25)
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| Chemical Name |
3-(6-((4-(trifluoromethoxy)phenyl)amino)pyrimidin-4-yl)benzamide
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6715 mL | 13.3576 mL | 26.7151 mL | |
| 5 mM | 0.5343 mL | 2.6715 mL | 5.3430 mL | |
| 10 mM | 0.2672 mL | 1.3358 mL | 2.6715 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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GNF-2 induces translocation of the myristoylated c-Abl to the ER.J Biol Chem.2009 Oct 16;284(42):29005-14. |
N-Myristoyl group in c-Abl affects the ability of GNF-2 to inhibit c-Abl kinase activity.J Biol Chem.2009 Oct 16;284(42):29005-14. |
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