MCE products for research use only. We do not sell to patients.

Axitinib

MCE China：Axitinib

Brand：MedChemExpress (MCE)

Cat. No.HY-10065

CAS：319460-85-0

Synonyms：AG-013736

Purity：99.90%

Storage：Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year

Shipping：Room temperature in continental US; may vary elsewhere.

Description：Axitinib is a multi-targeted tyrosine kinase inhibitor with IC50s of 0.1, 0.2, 0.1-0.3, 1.6 nM for VEGFR1, VEGFR2, VEGFR3 and PDGFRβ, respectively.

In Vitro：Axitinib (AG-013736) is a potent and selective inhibitor of VEGFR 1 to 3. In transfected or endogenous RTK-expressing cells, Axitinib potently blocks growth factor-stimulated phosphorylation of VEGFR-2 and VEGFR-3 with average IC50 values of 0.2 and 0.1 to 0.3 nM, respectively. Cellular activity against VEGFR-1 is 1.2 nM (measured in the presence of 2.3% bovine serum albumin), equivalent to an absolute IC50 of ~0.1 nM, based on protein binding of Axitinib. The potency against murine VEGFR-2 (Flk-1) in Flk-1-transfected NIH-3T3 cells is 0.18 nM, similar to that of its human homologue. Axitinib shows ~8- to 25-fold higher IC50 against the closely related type III and V family RTKs, including PDGFR-β (1.6 nM), KIT (1.7 nM), and PDGFR-α (5 nM); nanomolar concentrations of Axitinib blocks PDGF BB-mediated human glioma U87MG cell (PDGFR-β-positive) migration but not proliferation[2].

In Vivo：A single oral dose of Axitinib (100 mg/kg) markedly suppresses murine VEGFR-2 phosphorylation for up to 7 h compared with control tumors. Axitinib rapidly inhibits VEGF-induced vascular permeability in the skin of mice; the inhibition is dose-dependent and directly correlated with drug concentration in mice. Pharmacokinetic/pharmacodynamic analysis indicate an unbound EC50 of 0.46 nM. Similar inhibitory effects are also shown in the skin of MV522 tumor-bearing mice without exogenous VEGF-A stimulation. Axitinib inhibits the growth of human xenograft tumors in mice. Axitinib produces dose-dependent growth delay regardless of initial tumor size, model type, or implant site[2].

Animal Administration：Mice and Rats[2] Mice with M24met xenograft tumors (400-600 mm3) are administered with a single dose of Axitinib or the control (0.5% carboxymethylcellulose/H2O). Blood and tumor tissue samples are collected for pharmacokinetic and VEGFR-2 measurements. Total protein concentrations in tumor tissues are determined using the Bradford colorimetric assay. Six-day-old Sprague-Dawley rats are given two i.p. injections of Axitinib (30 mg/kg ). Animals are sacrificed, retinas are collected and lysed, and immunoprecipitation/immunoblotting experiments are done. ECL-Plus is used for detection and densitometry analysis is done using the Alpha Imager 8800.

Cell Assay：Endothelial or tumor cells are starved for 18 h in the presence of either 1% FBS (HUVEC) or 0.1% FBS (tumor cells). Axitinib is added and cells are incubated for 45 min at 37°C in the presence of 1 mM Na3VO4. The appropriate growth factor is added to the cells, and after 5 min, cells are rinsed with cold PBS and lysed in the lysis buffer and a protease inhibitor cocktail. The lysates are incubated with immunoprecipitation antibodies for the intended proteins overnight at 4°C. Antibody complexes are conjugated to protein A beads and supernatants are separated by SDS-PAGE[2].

IC50 & Target：VEGFR1 0.1 nM (IC50) VEGFR2 0.2 nM (IC50) VEGFR3 0.1 nM (IC50) PDGFRβ 1.6 nM (IC50)

Hot selling product：Eravacycline (dihydrochloride)  | Methicillin (sodium salt)  | Ginkgolic Acid  | Guselkumab  | SCH-23390 (hydrochloride)  | Belumosudil  | Colcemid  | AU-15330  | Tetracycline  | DMH-1

Trending products：Recombinant Proteins  |  Bioactive Screening Libraries  |  Natural Products  |  Fluorescent Dye  |  PROTAC  |  Isotope-Labeled Compounds  |  Oligonucleotides

References：

[1]. Fenton BM, et al. The addition of AG-013736 to rractionated radiation improves tumor response without functionally normalizing the tumor vasculature. Cancer Res. 2007 Oct 15;67(20):9921-8.  [Content Brief]

[2]. Hu-Lowe DD, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008 Nov 15;14(22):7272-83  [Content Brief]

[3]. Allen E, et al. Metabolic Symbiosis Enables Adaptive Resistance to Anti-angiogenic Therapy that Is Dependent on mTOR Signaling. Cell Rep. 2016 May 10;15(6):1144-60.  [Content Brief]