Fruquintinib|HMPL-013 Chemical Properties

Boiling point:

600.5±55.0 °C(Predicted)

Density 

1.302±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

Soluble in DMSO (up to 5 mg/ml).

pka

14.35±0.46(Predicted)

form 

solid

color 

White

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 month.

Fruquintinib|HMPL-013 Usage And Synthesis

Description

Fruquintinib is a VEGFR inhibitor (IC₅₀s = 33, 35, and 0.5 nM for VEGFR1, -2, and -3, respectively). It also inhibits RET, FGFR1, and c-Kit (IC₅₀s = 128, 181, and 458 nM, respectively) in a panel of 253 kinases. Fruquintinib inhibits VEGF-A-induced proliferation of human umbilical vein endothelial cells (HUVECs) and VEGF-C-induced proliferation of human lymphatic endothelial cells (HLECs; IC₅₀s = 1.7 and 4.2 nM, respectively). It decreases tube formation by HUVECs by 74 and 94% when used at concentrations of 30 and 300 nM, respectively. Fruquintinib (0.5-20 mg/kg per day for 21 days) reduces tumor growth in BGC-823, HT-29, Caki-1, and NCI H460 mouse xenograft models.

Uses

Fruquintinib is a multi-targeted tyrosine kinase inhibitor, a third-line regimen involved in the treatment of advanced non-small cell lung cancer in humans. Fruquintinib is a potent, highly selective and orally active inhibitor of VEGFR1, 2, 3 tyrosine kinases.

in vitro

fruquintinib was found to inhibit vegfr2 with an ic50 of 25 nmol/l. the kinase selectivity of fruquintinib was evaluated against a panel of 253 kinases. the results showed that fruquintinib inhibited vegfr family members with weak inhibition of ret, fgfr-1 and c-kit kinases [1].

in vivo

anti-tumor activity of fruquintinib was evaluated in a variety of tumor xenografts. the results from gastric cancer bgc-823 model seemed to indicate that the drug concentration needs to be at least maintained above ec85 for around 8 hours in order to achieve >80% tumor growth inhibition. bgc-823 was found to be most sensitive to fruquintinib [1].

IC 50

33 nmol/l, 35 nmol/l and 0.5 nmol/l for vegfr1, 2, 3

References

1) Sun?et al.?(2014)?Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1,2,3 tyrosine kinases for cancer therapy; Cancer Biol. Ther.?15?1635 2) Li?et al.?(2018)?Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial; JAMA?319?2486 3) Lu?et al.?(2018)?Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase II Study of Fruquintinib After Two Prior Chemotherapy Regimens in Chinese Patients With Advanced Nonsquamous Non-Small-cell Lung Cancer; J. Clin. Oncol.?36?1207

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