GNF-7
IC50:The IC50 of GNF-7is 0.005, 0.001, and 0.008 µM in Colo205, SW620, and TrkC-Ba/F3 cells, respectively.
GNF-7 is the type-II inhibitor of T315I-Bcr-Abl [1]. BCR-ABL, constitutively activated tyrosine kinase, is an oncogene associated with chronic myelogenous leukemia (CML) and some cases ofacute lymphocytic leukemia in humans.
In vitro:GNF-7 showed excellent growth inhibitory activity against some human cancer cells. The IC50 of GNF-7is 0.005, 0.001, and 0.008 µM when tested in Colo205, SW620, and TrkC-Ba/F3 cell line, respectively.GNF-7 showed little effect on HEK293T cells, a normal cell line [1].After treated for 24h (7.5mg/kg QD or 15 mg/kg QD), GNF-7 significantly decreaseddisease burden in mice and prolonged overall survival compared to vehicle-controls [2].
In vivo:In acute myelogenous leukemia and lymphoblastic leukemia models, GNF-7 potently and selectively inhibited NRAS-dependent cells [2]. In theT315I-Bcr-Abl-Ba/F3 cell line bioluminescent xenograft mouse model,oral administration of GNF-7 with 10or20mg/kgexhibited significant efficacy against T315I-Bcr-Abl without appreciable toxicity [1].
References:
Choi H G, Ren P, Adrian F, et al. A type-II kinase inhibitor capable of inhibiting the T315I “gatekeeper” mutant of Bcr-Abl[J]. Journal of medicinal chemistry, 2010, 53(15): 5439-5448.
Nonami A, Sattler M, Weisberg E, et al. Identification of novel therapeutic targets in acute leukemias with NRAS mutations using a pharmacologic approach[J]. Blood, 2015, 125(20): 3133-3143.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 547.53 |
| Cas No. | 839706-07-9 |
| Formula | C28H24F3N7O2 |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥5.48 mg/mL in DMSO |
| Chemical Name | (Z)-N-(4-methyl-3-(1-methyl-7-((6-methylpyridin-3-yl)amino)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)benzimidic acid |
| SDF | Download SDF |
| Canonical SMILES | CC1=C(N(C2=O)CC(C(N2C)=N3)=CN=C3NC4=CN=C(C=C4)C)C=C(/N=C(O)/C5=CC(C(F)(F)F)=CC=C5)C=C1 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
Quality Control & MSDS
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Chemical structure
