product name GNF-7
Description: GNF-7 is a novel, potent, oral bioactive type-II kinase Bcr-Abl inhibitor with IC50 of <5 nM, 61 nM, 122 nM, 136 nM, and 133 nM for M351T, T315I, E255 V, G250E, and c-Abl, respectively. GNF-7 displayed significant in vivo efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. GNF-7 is among the first type-II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design the third generation Bcr-Abl kinase inhibitors.
References: J Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43.
547.53
Formula
C28H24F3N7O2
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
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19400696
| 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: Cell Assay: |
|---|---|
| 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. |
| Animal model | SCID beige female mice bearing T315I-Bcr-Abl-Ba/F3 orthotopic xenografts |
| Formulation & Dosage | Dissolved in DMSO; 20 mg/kg; Oral gavage |
| References | J Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43. |
Related Posts
product name GNF-7
Description: GNF-7 is a novel, potent, oral bioactive type-II kinase Bcr-Abl inhibitor with IC50 of <5 nM, 61 nM, 122 nM, 136 nM, and 133 nM for M351T, T315I, E255 V, G250E, and c-Abl, respectively. GNF-7 displayed significant in vivo efficacy against T315I-Bcr-Abl without appreciable toxicity in a bioluminescent xenograft mouse model using a transformed T315I-Bcr-Abl-Ba/F3 cell line that has a stable luciferase expression. GNF-7 is among the first type-II inhibitors capable of inhibiting T315I to be described and will serve as a valuable lead to design the third generation Bcr-Abl kinase inhibitors.
References: J Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43.
547.53
Formula
C28H24F3N7O2
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
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19400696
| 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: Cell Assay: |
|---|---|
| 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. |
| Animal model | SCID beige female mice bearing T315I-Bcr-Abl-Ba/F3 orthotopic xenografts |
| Formulation & Dosage | Dissolved in DMSO; 20 mg/kg; Oral gavage |
| References | J Med Chem. 2010 Aug 12;53(15):5439-48; Blood. 2015 May 14;125(20):3133-43. |