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Fruquintinib
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。
Fruquintinib图片
CAS NO:1194506-26-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 393.39
Formula C21H19N3O5
CAS No. 1194506-26-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 6 mg/mL (15.2 mM)
Water: <1mg/mL
Ethanol:<1mg/mL
Chemical Name 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide
Synonyms HMPL-013; HMPL 013; HMPL013
实验参考方法
In Vitro

In vitro activity: Fruquintinib (formerly known as HMPL-013) is a novel, potent, selective and oral small molecule inhibitor with strong potency and high selectivity against VEGFR family. It is currently in Phase II clinical studies. Analysis of Phase I pharmacokinetic data revealed that at the maximum tolerated dose of once daily oral administration fruquintinib achieved complete VEGFR2 suppression (drug concentrations were maintained above that required to produce>85% inhibition of VEGFR2 phosphorylation in mouse) for 24 hours/day. VEGF/VEGFR signal axis has been proven to be an important target for development of novel cancer therapies. One challenging aspect in small molecular VEGFR inhibitors is to achieve sustained target inhibition at tolerable doses previously seen only with the long-acting biologics. It would require high potency (low effective drug concentrations) and sufficient drug exposures at tolerated doses so that the drug concentration can be maintained above effective drug concentration for target inhibition within the dosing period.


Kinase Assay: In in vitro enzymatic and cellular assays, Fruquintinib inhibits VEGFR family kinases and suppressed VEGF/VEGFR cell signaling in human umbilical vein endothelial cell (HUVEC) and human lymphatic endothial cell (HLEC) with IC50 at low nanomolar level. Few kinases are inhibited other than VEGFRs in a panel of 253 kinases test. Fruquintinib is a highly potent inhibitor of VEGF-induced angiogenesis.


Cell Assay: Primary HUVECs or HLECs in exponential phase are suspended in 100 μL of RPMI-1640 media containing 0.5% FBS, and seeded at 5000 cell/well in 96-well plates pre-coated with 0.2% gelatin or fibronectin, and incubated overnight in a 5% CO2, 37°C incubator. Fruquintinib and VEGF-A165 or VEGF-C (50 ng/mL) are added and incubated for 48 hours. Viability of the cells is determined using CCK-8 assay format.

In VivoIn Gastric cancer BGC-823 model, fruquintinib inhibits tumor growth by 62.3% and 95.4~98.6%, at 0.5 and 2 mg/kg once daily dosing, respectively. When the dose is elevated to 5 mg/kg and 20 mg/kg, the tumors regress by 24.1% and 48.6%, respectively. The level of anti-tumor growth activity of fruquintinib varies in different tumor xenograft models. Fruquintinib significantly decreases the micro-vessel density even at the lowest dose of 0.8 mg/kg
Animal model Female Balb/c nude mice with Gastric cancer BGC-823 model
Formulation & Dosage 0.5% aqueous CMC-Na; 2.5 mg/kg; p.o.
References Cancer Biol Ther. 2014;15(12):1635-45.