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    InvivoChem Cat #: V0672
    CAS #: 839706-07-9Purity ≥98%

    Description: GNF-7 (GNF7; GNF 7) is a novel, potent, orally bioactive/bioavailable Bcr-Abl kinase inhibitor with potential anticancer activity. It inhibits the following kinases: M351T, T315I, E255 V, G250E and c-Abl, with IC50s of<5 nM, 61 nM, 122 nM, 136 nM, and 133 nM, respectively. It demonstrate significant in vivo antitumor efficacy in SCID beige female mice bearing T315I-Bcr-Abl-Ba/F3 orthotopic xenografts.

    References: J Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43.

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    Molecular Weight (MW)547.53
    CAS No.839706-07-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 20 mg/mL (36.5 mM) 
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Other infoChemical Name: N-(4-methyl-3-(1-methyl-7-((6-methylpyridin-3-yl)amino)-2-oxo-1,4-dihydropyrimido[4,5-d]pyrimidin-3(2H)-yl)phenyl)-3-(trifluoromethyl)benzamide
    InChi Code: InChI=1S/C28H24F3N7O2/c1-16-7-9-21(34-25(39)18-5-4-6-20(11-18)28(29,30)31)12-23(16)38-15-19-13-33-26(36-24(19)37(3)27(38)40)35-22-10-8-17(2)32-14-22/h4-14H,15H2,1-3H3,(H,34,39)(H,33,35,36)
    SMILES Code: O=C(NC1=CC=C(C)C(N2CC3=CN=C(NC4=CC=C(C)N=C4)N=C3N(C)C2=O)=C1)C5=CC=CC(C(F)(F)F)=C5
    SynonymsGNF7; GNF 7; GNF-7; 

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    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.

    In VivoGNF-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.
    Animal modelSCID beige female mice bearing T315I-Bcr-Abl-Ba/F3 orthotopic xenografts
    Formulation & DosageDissolved in DMSO; 20 mg/kg; Oral gavage
    ReferencesJ Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


    Effect of GNF-7 suppression of AKT and/or GCK on induction of apoptosis and cell cycle. Blood. 2015 May 14; 125(20): 3133–3143.


    In vivo efficacy of GNF-7 in a xenotransplantation model and activity against primary AML patient samples. Blood. 2015 May 14; 125(20): 3133–3143.


    Identification of GCK as a functionally relevant target of GNF-7. Blood. 2015 May 14;125(20):3133-43.


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