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Purity: ≥98%
GNF-5 (GNF 5; GNF5), a GNF-2 analog with better pharmacokinetic profiles, is a potent, selective and allosteric/non-ATP competitive Bcr-Abl inhibitor with potential anticancer activity. It inhibits Bcr-Abl (wild-type Abl) with an IC50 of 220 nM. It exhibits excellent in vivo anticancer efficacy in Ba/F3.p210 xenograft mouse model.
| ln Vitro |
GNF-5 inhibits wild-type Abl with an IC50 of 0.22 µM, but not myristate site mutant E505K (IC50 ＞10 µM) [1].
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| ln Vivo |
GNF-5 has appropriate pharmacokinetic properties (5 mg/kg IV or 20 mg/kg oral)[1]. GNF-5 is effective in vivo when taken orally, twice daily for seven days at 50 or 100 mg/kg, however relapses are possible[1]. In vivo, nilotinib with T315I Bcr-Abl combo is inhibited by GNF-5 (75 mg/kg, bid)[1].
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: wild type and mutant Bcr- Abl expressing Ba/F3 cells Tested Concentrations: 0.2, 0.8 and 1.6 μM Incubation Duration: 48 h Experimental Results: Inhibited wild-type Abl in a non-ATP competitive fashion. |
| Animal Protocol |
Animal/Disease Models: Male balb/c (Bagg ALBino) mouse[1]
Doses: 5 mg/kg, 20 mg/kg Route of Administration: 5 mg/kg intravenously (iv)or 20 mg/kg orally Experimental Results: AUC_inf (min*ug/mL) 292.37 AUC_inf (hrs*nM 11647 Cmax(nM) 4386.08 Tmax(hrs) 0.50 Clast (nM) 636.16 T1 /2(hrs) 2.30 Vss(L/kg) 9.18 F (%) 44.82 Animal/Disease Models: p210 xenograft model[1] Doses: 50 or 100 mg/kg Route of Administration: po (oral gavage) twice (two times) daily, for 7 days Experimental Results: Could normalize blood counts and spleen size. Animal/Disease Models: Bone marrow transduction/transplantation model[1] Doses: 75 mg/kg Route of Administration: twice (two times) daily Experimental Results: demonstrated no significant response (alone). demonstrated no toxicity and had a strong and sustained inhibition of Bcr- Abl-mediated signaling combination with nilotinib. |
| References |
[1]. Zhang J, et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010 Jan 28;463(7280):501-6.
[2]. Meirson T, et al. Targeting invadopodia-mediated breast cancer metastasis by using ABL kinase inhibitors. Oncotarget. 2018 Apr 24;9(31):22158-22183. |
| Molecular Formula |
C20H17F3N4O3
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| Molecular Weight |
418.37
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| CAS # |
778277-15-9
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| Related CAS # |
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| SMILES |
FC(OC1C([H])=C([H])C(=C([H])C=1[H])N([H])C1C([H])=C(C2C([H])=C([H])C([H])=C(C(N([H])C([H])([H])C([H])([H])O[H])=O)C=2[H])N=C([H])N=1)(F)F
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| InChi Key |
IIQUYGWWHIHOCF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H17F3N4O3/c21-20(22,23)30-16-6-4-15(5-7-16)27-18-11-17(25-12-26-18)13-2-1-3-14(10-13)19(29)24-8-9-28/h1-7,10-12,28H,8-9H2,(H,24,29)(H,25,26,27)
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| Chemical Name |
N-(2-Hydroxyethyl)-3-[6-[[4-(trifluoromethoxy)phenyl]amino]-4-pyrimidinyl]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 (5.98 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 (5.98 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 (5.98 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 | 2.3902 mL | 11.9511 mL | 23.9023 mL | |
| 5 mM | 0.4780 mL | 2.3902 mL | 4.7805 mL | |
| 10 mM | 0.2390 mL | 1.1951 mL | 2.3902 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.
Cellular and enzymatic inhibition of wild-type and mutants by combination treatments.Nature.2010 Jan 28;463(7280):501-6. |
In vivo efficacy studies with GNF-5 on wild-type and T315I Bcr-Abl dependent proliferation in xenograft and bone marrow transplantation models.Nature.2010 Jan 28;463(7280):501-6. |
Hydrogen exchange mass spectrometry upon binding of GNF-5 to Abl.Nature.2010 Jan 28;463(7280):501-6. |
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