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CAS No. : 839706-07-9
|Size||Stock||Price||Quantity||Add to Cart||Quotation Online|
|5mg||In-stock||USD 108.0 108.0|
|10mg||In-stock||USD 180.0 180.0|
|25mg||In-stock||USD 360.0 360.0|
|50mg||In-stock||USD 648.0 648.0|
|100mg||In-stock||USD 1152.0 1152.0|
|Cat. No. :||CS-5551|
|CAS No. :||839706-07-9|
|M. Wt. :||547.53|
|Solubility:||DMSO : ≥ 33 mg/mL|
GNF-7 is a multikinase inhibitor. GNF-7 is a Bcr-Abl inhibitor, with IC50s of 133 nM and 61 nM for Bcr-AblWT and Bcr-AblT315I, respectively. GNF-7 also possesses inhibitory activity against both ACK1 (activated CDC42 kinase 1) and GCK (germinal center kinase) with IC50s of 25 nM and 8 nM, respectively. GNF-7 can be used for the research of hematologic malignancies.
IC50 & Target: IC50: 133 nM (Bcr-AblWT), 61 nM (Bcr-AblT315I), 25 nM (ACK1), 8 nM (GCK)
In Vitro: GNF-7 potently inhibits wild-type Bcr-Abl (IC50<5 nM) and Bcr-Abl mutants such as T315I (IC50=11 nM), G250E (IC50<5 nM), E255V (IC50=10 nM), F317L (IC50<5 nM) and M351T (IC50<5 nM) in cellular assays.
GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream.
GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines.
In Vivo: GNF-7 (10-20 mg/kg; o.p.; daily; for 7 days) displays significant in vivo efficacy against T315I Bcr-Abl in the bioluminescent xenograft mouse model.
GNF-7 exhibits moderate oral bioavailability (mice 36%) and Cmax (mice 3616 nM) following oral administration (mice 20 mg/kg).
GNF-7 exhibits terminal elimination half-lives (mice 3.8 h) due to high plasma clearance (8.6 mL/min/kg) following intravenous injection (mice 5 mg/kg).
Protocol:Animal administration  GNF-7 was dissolved in a 100% PEG300 solution formulation (2.5 mg/mL) and dosed at 5 mg/kg intravenously via the lateral vein (n=3). Five to six week old male Balb/c mice (20-25 g) were obtained from Jackson Laboratory. The oral dose was prepared in a 1:1 formulation of PEG300 and distilled water and administered at 20 mg/kg via oral gavage (n=3). Five blood samples (50 μL) were serially drawn via retro orbital sinus within 24 hours after dosing. Plasma concentrations of GNF-7 were quantified utilizing a Liquid Chromatography/Mass Spectrometry (LC/MS/MS) assay. Pharmacokinetic parameters were calculated by non-compartmental regression analysis using Winnonlin 4.0 software.
Cho, H., et al. First SAR study for overriding NRAS mutant driven acute myeloid leukemia. Journal of Medicinal Chemistry.
Lu X, et al. Hybrid pyrimidine alkynyls inhibit the clinically resistance related Bcr-Abl(T315I) mutant. Bioorg Med Chem Lett. 2015 Sep 1;25(17):3458-63.
Choi HG, et al. A type-II kinase inhibitor capable of inhibiting the T315I "gatekeeper" mutant of Bcr-Abl. J Med Chem. 2010 Aug 12;53(15):5439-48.
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