WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206175
CAS#: 1194506-26-7
Description: Fruquintinib, also known as HMPL-013, is an orally available, small molecule inhibitor of vascular endothelial growth factor receptors (VEGFRs), with potential anti-angiogenic and antineoplastic activities. Upon oral administration, fruquintinib inhibits VEGF-induced phosphorylation of VEGFRs 1, 2, and 3 which may result in the inhibition of migration, proliferation and survival of endothelial cells, microvessel formation, the inhibition of tumor cell proliferation, and tumor cell death. Expression of VEGFRs may be upregulated in a variety of tumor cell types.
Hodoodo Cat#: H206175
Name: Fruquintinib
CAS#: 1194506-26-7
Chemical Formula: C21H19N3O5
Exact Mass: 393.13
Molecular Weight: 393.390
Elemental Analysis: C, 64.12; H, 4.87; N, 10.68; O, 20.34
Synonym: Fruquintinib; HMPL013; HMPL 013; HMPL-013.
IUPAC/Chemical Name: 6-((6,7-dimethoxyquinazolin-4-yl)oxy)-N,2-dimethylbenzofuran-3-carboxamide
InChi Key: BALLNEJQLSTPIO-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H19N3O5/c1-11-19(20(25)22-2)13-6-5-12(7-16(13)28-11)29-21-14-8-17(26-3)18(27-4)9-15(14)23-10-24-21/h5-10H,1-4H3,(H,22,25)
SMILES Code: O=C(C1=C(C)OC2=CC(OC3=C4C=C(OC)C(OC)=CC4=NC=N3)=CC=C12)NC
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Fruquintinib (HMPL-013) is a highly potent and selective VEGFR 1/2/3 inhibitor with IC50s of 33, 0.35, and 35 nM, respectively. |
| In vitro activity: | 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. Reference: Cancer Biol Ther. 2014;15(12):1635-45. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25482937/ |
| In vivo activity: | 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. Reference: Cancer Biol Ther. 2014;15(12):1635-45. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25482937/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 5.9 | 14.95 |
The following data is based on the product molecular weight 393.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Sun Q, Zhou J, Zhang Z, Guo M, Liang J, Zhou F, Long J, Zhang W, Yin F, Cai H, Yang H, Zhang W, Gu Y, Ni L, Sai Y, Cui Y, Zhang M, Hong M, Sun J, Yang Z, Qing W, Su W, Ren Y. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45. doi: 10.4161/15384047.2014.964087. PMID: 25482937; PMCID: PMC4622458. 2. Liu X, Guo A, Tu Y, Li W, Li L, Liu W, Ju Y, Zhou Y, Sang A, Zhu M. Fruquintinib inhibits VEGF/VEGFR2 axis of choroidal endothelial cells and M1-type macrophages to protect against mouse laser-induced choroidal neovascularization. Cell Death Dis. 2020 Nov 27;11(11):1016. doi: 10.1038/s41419-020-03222-1. PMID: 33247124; PMCID: PMC7695853. |
| In vivo protocol: | 1. Sun Q, Zhou J, Zhang Z, Guo M, Liang J, Zhou F, Long J, Zhang W, Yin F, Cai H, Yang H, Zhang W, Gu Y, Ni L, Sai Y, Cui Y, Zhang M, Hong M, Sun J, Yang Z, Qing W, Su W, Ren Y. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45. doi: 10.4161/15384047.2014.964087. PMID: 25482937; PMCID: PMC4622458. 2. Liu X, Guo A, Tu Y, Li W, Li L, Liu W, Ju Y, Zhou Y, Sang A, Zhu M. Fruquintinib inhibits VEGF/VEGFR2 axis of choroidal endothelial cells and M1-type macrophages to protect against mouse laser-induced choroidal neovascularization. Cell Death Dis. 2020 Nov 27;11(11):1016. doi: 10.1038/s41419-020-03222-1. PMID: 33247124; PMCID: PMC7695853. |
1: Sun Q, Zhou J, Zhang Z, Guo M, Liang J, Zhou F, Long J, Zhang W, Yin F, Cai H, Yang H, Zhang W, Gu Y, Ni L, Sai Y, Cui Y, Zhang M, Hong M, Sun J, Yang Z, Qing W, Su W, Ren Y. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014 Sep 24:0. [Epub ahead of print] PubMed PMID: 25482937.
2: Gu Y, Wang J, Li K, Zhang L, Ren H, Guo L, Sai Y, Zhang W, Su W. Preclinical pharmacokinetics and disposition of a novel selective VEGFR inhibitor fruquintinib (HMPL-013) and the prediction of its human pharmacokinetics. Cancer Chemother Pharmacol. 2014 Jul;74(1):95-115. doi: 10.1007/s00280-014-2471-3. Epub 2014 May 11. PubMed PMID: 24817647.
