Fruquintinib (HMPL-013) 是有效，选择性的 VEGFR 1/2/3 抑制剂，IC50 值分别为33，0.5，and 35 nM。
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Molecular Weight |
393.39 | ||||||||||||
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Formula |
C₂₁H₁₉N₃O₅ | ||||||||||||
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CAS No. |
1194506-26-7 | ||||||||||||
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Storage |
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Shipping |
Room temperature in continental US; may vary elsewhere | ||||||||||||
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Solvent & Solubility |
DMSO: 7.75 mg/mL * “<1 mg/mL” means slightly soluble or insoluble. “≥” means soluble, but saturation unknown. |
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Description |
Fruquintinib (HMPL-013) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC50s of 33, 0.35, and 35 nM, respectively. | ||||||||||||||||
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IC50 & Target |
IC50: 33 nM (VEGFR 1), 0.5 nM (VEGFR 2), 35 nM (VEGFR 3) | ||||||||||||||||
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In Vitro |
Fruquintinib demonstrates potent inhibition on VEGF-A dependent KDR phosphorylation in HEK293-KDR cells and VEGF-A induced proliferation in primary HUVECs with IC50s of 0.6±0.2 nM and 1.7 nM, respectively. Similarly, potent VEGFR3 attenuation by fruquintinib is observed in primary HLECs, with IC50s of 1.5 nM and 4.2 nM for VEGF-C stimulated VEGFR3 phosphorylation and proliferation, respectively. Fruquintinib suppresses the tube branching, tube length and area in a concentration-dependent manner. The tubule length of primary HUVECs decreased by 74% and 94% at 0.03 and 0.3 μM of fruquintinib, respectively. Fruquintinib inhibits HUVEC tubule growth and CAM angiogenesis. Tube formation is suppressed significantly after treatment with fruquintinib at 0.3 μM for 18 hours. | ||||||||||||||||
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In Vivo |
Gastric cancer BGC-823 model is found to be most sensitive to fruquintinib. In this 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 | ||||||||||||||||
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Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent. |
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Cell Assay |
Fruquintinib is prepared initially as a 10 mM stock solution in DMSO and diluted in appropriate assay media. 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. |
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Animal Administration |
Fruquintinib is suspended in aqueous 0.5% CMC-Na (w/v) and stored at 4°C. Mouse: The patient derived xenograft models are established after the primary tumor adopted serial passages in vivo. Once tumors have grown to 100-300 mm3, the animals are randomly assigned with 6-8 animals per group. The mice are treated orally with the vehicle (control group) or fruquintinib at a dose range of 0.5-20 mg/kg suspended in the vehicle (treated group) once daily for 3 weeks. In combination studies, docetaxel (Taxotere, 5 mg/kg) or oxaliplatin (10 mg/kg) is administered to nude mouse via intravenous injection, once a week. Tumor size and body weights are measured 3 times a week. Tumor volumes (TV) are calculated |
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