AxitinibLicensed by Pfizer Catalog No.S10

 Axitinib

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

Biological Activity

Description	Axitinib is a multi-target inhibitor of VEGFR1, VEGFR2, VEGFR3, PDGFRβ and c-Kit with IC50 of 0.1 nM, 0.2 nM, 0.1-0.3 nM, 1.6 nM and 1.7 nM, respectively.
Targets	VEGFR1	VEGFR2	VEGFR3	PDGFRβ	c-Kit
IC50	0.1 nM	0.2 nM	0.1-0.3 nM	1.6 nM	1.7 nM [1]
In vitro	Axitinib could block the cellular autophosphorylation of VEGFR and VEGF-mediated endothelial cell viability, tube formation, and downstream signaling. Axitinib inhibits the proliferation of variable cell lines with IC50 of >10,000 nM (IGR-N91), 849 nM (IGR-NB8), 274 nM (SH-SY5Y) and 573 nM (non-VEGF stimulated HUVEC). [2]
In vivo	Axitinib exhibits primary inhibition to orthotopically transplanted models such as M24met (melanoma), HCT-116 (colorectal cancer), and SN12C (renal cell carcinoma). [1] Axitinib delays the tumor growth with 11.4 days compared to the controls (p.o. 30 mg/kg) and decreases the Mean Vessels Density (MVD) to 21, compared to 49 in controls, in IGR-N91 flank xenografts. [2] Axitinib significantly inhibits growth and disrupts tumor microvasculature in BT474 breast cancer model at 10-100 mg/kg. [3] Axitinib has shown single-agent activity in variable tumors, including renal cell carcinoma, thyroid cancer, non-small cell lung cancer, and melanoma.
Features	Superior as second-line therapy relative to sorafenib (current standard-of-care).

Protocol(Only for Reference)

Kinase Assay: 

^[1]

Cellular receptor kinase phosphorylation assay

Porcine aorta endothelial (PAE) cells, which overexpress full-length VEGFR2, PDGFRβ, Kit, and NIH-3T3, which overexpress murine VEGFR2 (Flk-1) or PDGFRα, are generated. The 96-well plates are coated with 100 μL/well of 2.5 μg/mL anti-VEGFR2 antibody, 0.75 μg/mL anti-PDGFRβ antibody, 0.25 μg/mL anti-PDGFRα antibody, 0.5 μg/mL anti-KIT antibody, or 1.20 μg/mL anti-Flk-1 antibody to prepare ELISA capture plates. Then phosphorylation of RTK is measured by ELISA.

Cell Assay: 

^[2]

Cell lines	HUVEC, SH-SY5Y, IGR-N91 and IGR-NB8 cells
Concentrations	1 nM - 10 μM
Incubation Time	72 hours
Method	Cells are seeded in a 96-well plate at a density of 5 × 104 and cultured for 24 hours. Axitinib is added to the cells at concentrations ranging from 1 nM to 10 μM. Cell viability is measured after 72 hours by MTS tetrazolium substrate and IC50 values are calculated.

Animal Study: 

^[3]

Animal Models	BT474 breast cancer cells are implanted subcutaneously into Immune-deficient female mice (Nu/nu; age 8-12 weeks).
Dosages	10, 30 or 100 mg/kg
Administration	Oral daily
Solubility	0.5% CMC, 30 mg/mL

1

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01727336	Recruiting	Advanced Renal Cell Carcinoma	Acceleron Pharma, Inc.	2012-12	Phase 2
NCT01798446	Recruiting	Renal Cell Carcinoma|Nonclear Cell|Temsirolimus Resistance	Seoul National University Hospital|Pfizer	2013-02	Phase 2
NCT01806064	Recruiting	Renal Cell Carcinoma	Tracon Pharmaceuticals Inc.	2013-03	Phase 1
NCT01967576	Recruiting	Pheochromocytoma|Paraganglioma	National Institutes of Health Clinical Center (CC)|National Cancer Institute (NCI)	2013-10	Phase 2
NCT01999972	Not yet recruiting	Advanced Solid Tumors	Pfizer	2013-12	Phase 1

Chemical Information

Download Axitinib SDF

Chemical Name

Customer Reviews (4)

Click to enlarge	Rating
	Source	J Biomol Screen 2011 16, 141-154. Axitinib purchased from Selleck
	Method	Spheroid staining and sectioning
	Cell Lines	MDA-MB-231 cells
	Concentrations	10 µM
	Incubation Time	72 h
	Results	Significant down-regulation of vimentin protein expression was observed throughout the outer surface of U0126-treated spheroids as visualized by 3d confocal microscopy (Fig. A). to measure the extent of penetration into the spheroid by U0126 or axitinib, spheroids were sectioned and stained for vimentin (Fig. B,C). these results demonstrate that both U0126 and axitinib penetrated into the spheroid, resulting in downregulation of vimentin throughout the whole spheroid by more than 80% as compared to untreated spheroids.

Product Citations (9)

• 
  

  Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A. [Martin MJ, et al. Cancer Discov 2012;2(4):344-55]

  
  PubMed: 22576211


• 
  

  Growth factor-mediated mesodermal cell guidance and skeletogenesis during sea urchin gastrulation. [Adomako-Ankomah A, et al. Development 2013;140(20):4214-25]

  
  PubMed: 24026121


• 
  

  Impact of vegf on astrocytes: Analysis of gap junctional intercellular communication, proliferation, and motility. [Wuestefeld R, et al. Glia 2012;60(6):936-47]

  
  PubMed: 22431192