GNF-7

GNF-7 is a multikinase inhibitor. GNF-7 is a Bcr-Abl inhibitor, with IC₅₀s of 133 nM and 61 nM for Bcr-Abl^WT and Bcr-Abl^T315I, 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^[1][2][3]. IC50 & Target:IC50: 133 nM (Bcr-Abl^WT)^[1], 61 nM (Bcr-Abl^T315I)^[1], 25 nM (ACK1)^[3], 8 nM (GCK)^[3] 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^[2].
GNF-7 (1 μM; 2 hours) suppresses AKT/mTOR signaling and GCK downstream^[3].
GNF-7 (1 μM; 24 hours) induces of apoptosis and cell cycle arrest in NRAS mutant cell lines^[3].
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^[2].
GNF-7 exhibits moderate oral bioavailability (mice 36%) and C_max (mice 3616 nM) following oral administration (mice 20 mg/kg)^[2].
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)^[2].