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Flumatinib mesylate(HHGV-678)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Flumatinib mesylate(HHGV-678)图片
CAS NO:895519-91-2
规格:≥98%
包装与价格:
包装价格(元)
100mg电议
250mg电议
500mg电议
1g电议
2g电议
5g电议
10g电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 658.69
Formula C30H33F3N8O4S
CAS No. 895519-91-2 (mesylate); 895519-90-1 (free base)
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: ≥ 32 mg/mL
Water: N/A
Ethanol: N/A
Chemical NameN-(6-methyl-5-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)pyridin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide mesylate
SynonymsHHGV678 mesylate; HHGV 678 mesylate ; HHGV-678 mesylate; HH-GV-678 mesylate
SMILES CodeO=C(NC1=CC(NC2=NC=CC(C3=CC=CN=C3)=N2)=C(C)N=C1)C4=CC=C(CN5CCN(C)CC5)C(C(F)(F)F)=C4.CS(=O)(O)=O
实验参考方法
In Vitro

In vitro activity: HH-GV-678 can predominantly inhibit the autophosphorylation of Bcr-Abl in K562 cell. In higher concentration, HH-GV-678 can inhibit the phosphorylation of c-Kit in Mo7e cell and the phosphorylation of PDGFR in Swiss3T3 cell, however, HH-GV-678 has no or little effect on other tyrosine kinase including EGFR, KDR, c-Src and HER2. Flumatinib effectively overcame the drug resistance of certain KIT mutants with activation loop mutations (i.e., D820G, N822K, Y823D, and A829P).


Kinase Assay: Murine stem cell virus-based retroviral constructs carrying murine–human hybrid WT KIT cDNA or activating mutant D816V (816 Asp→Val) KIT cDNA were generously provided by Michael H. Tomasson (Washington University School of Medicine, St. Louis, MO, USA). Hybrid KIT alleles were generated by fusing in-frame the extracellular and transmembrane regions of murine KIT with the intracellular region of human KIT. It has been shown that replacement of the human extracellular and transmembrane domains of KIT with homologous murine sequences can improve the expression efficiency and rescue the transforming potential of certain KIT mutants in murine cells. Owing to a downstream internal ribosomal entry site–enhanced GFP cassette, KIT alleles would coexpress with enhanced GFP. The KIT point mutations were generated following Protocol 3 of mutagenesis in Molecular Cloning (3rd edition). For deletion and insertion mutagenesis, mutagenic primers were designed to avoid the deleted sequence or harbor the inserted sequence, respectively. All the PCRs above used the high-fidelity Primestar Hot Start DNA Polymerase (Takara, Dalian, China). Other enzymes used in above experiments were also purchased from Takara. The sequences of all mutants in this study were verified by direct sequencing.


Cell Assay: Cells (5 × 103) in 200 μL medium with or without IL-3 were incubated with various concentrations of imatinib, flumatinib, or sunitinib in 96-well plates for 72 h in triplicate. We added MTT, and cells were incubated for 4 h. A solubilization solution (a solution of the detergent SDS in diluted hydrochloric acid) was added to dissolve the insoluble purple formazan product into a colored solution. The absorbance of this colored solution was quantified by measuring at 570 nm with a reference filter of 650 nm by a spectrophotometer. Growth inhibition was plotted as the ratio of the average absorbance in drug-treated wells relative to no-drug controls. The IC50 values were calculated by the curve-fitting software GraphPad Prism version 5.

In VivoSix-week-old female Balb/cA-nu/nu mice weighing 17–19 g each were purchased from Shanghai SLAC Laboratory Animal Co., Ltd (Shanghai, China), and raised under specific pathogen-free conditions. Each mouse was injected s.c. with 1 × 107 KIT mutant transformed 32D cells in the right flank. Mice were randomized into groups (n = 8–10 per group) and treated by oral gavage with vehicle, imatinib, flumatinib, or sunitinib for the next 14 days.
Animal model Six-week-old female Balb/cA-nu/nu mice weighing 17–19 g bearing 32D-V559D or 32D-V559D+Y823D tumors
Formulation & Dosage 75mg/kg; Oral gavage
References Cancer Sci. 2014 Jan;105(1):117-25; Leukemia. 2010 Oct;24(10):1807-9.