| Protocol | In Vitro | In vitro activity: 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), GNF-7 also displays excellent growth inhibitory activity with IC50 of 5 nM and 1 nM, respectively. GNF-7, potently and selectively inhibits NRAS-dependent acute myelogenous leukemia and acute lymphoblastic leukemia cells through combined inhibition of ACK1/AKT and GCK. Kinase Assay: GNF-7 is amongst the first type II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design next generation Bcr-Abl kinase inhibitors. GNF-7 exhibits some selectivity (4 to 100-fold) for T315I Bcr-Abl (IC50 = 11 nM, in Ba/F3 cell line) relative to kinases such as TPR-Met, NPM-ALK, JAK-3, Flt-3. |
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| 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, GNF-7 (10 mg/kg, p.o.) effectively inhibits tumor growth. In NSG mice bearing human mutant NRAS-expressing MOLT-3-luc+ tumors, GNF-7 (15 mg/kg, p.o.) significantly decreases disease burden, prolongs overall survival, and causes strong suppression of phospho-AKT and phospho-RPS6. |
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| Animal model | SCID beige female mice bearing T315I-Bcr-Abl-Ba/F3 orthotopic xenografts |
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| Formulation | Dissolved in DMSO |
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| Dosages | 20 mg/kg; Oral gavage |
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These protocols are for reference only. InvivoChem does not
independently validate these methods.
Preparing Stock Solutions
| Solvent volume to be added |
Mass (the weight of a compound) |
| Mother liquor concentration |
1mg | 5mg | 10mg | 20mg |
| 1mM | 1.8264 mL | 9.1319 mL | 18.2638 mL | 36.5277 mL |
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| 5mM | 0.3653 mL | 1.8264 mL | 3.6528 mL | 7.3055 mL |
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| 10mM | 0.1826 mL | 0.9132 mL | 1.8264 mL | 3.6528 mL |
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| 20mM | 0.0913 mL | 0.4566 mL | 0.9132 mL | 1.8264 mL |
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Quality Control Documentation
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