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Axitinib Licensed by Pfizer

Axitinib (AG-013736) 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.

Catalog No.S1005

4 Reviews 5 Product Citations

: Tel: +1-832-582-8158[email protected]

Axitinib Chemical Structure
Molecular Weight: 386.47

Validation & Quality Control

Product Citations(5)

Cancer Discov, 2012, 2(4), 344-355

Glia, 2012, 60(6):936-47

Mol Med, 2012, 18:887-98

Cancer Sci, 2012, 103(3):433-8

J Biomol Screen, 2011, 16(2), 141-154

Customer Reviews(4) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Axitinib is available in the following compound libraries:

Inhibitor Library (96-well) Kinase Inhibitor Library (96-well) FDA Approved Drug Library (96-well) Chemical Library (96-well) Tyrosine Kinase Inhibitor Library (96-Well) Cambridge Cancer Compound Library(96-well) Pfizer Licensed Library

Product Information

Compare VEGFR Inhibitors

Research Area
Research Area
Axitinib Mechanism
Axitinib Mechanism
VEGFR2 consists of an extracellular region composed of seven immunoglobulin (Ig)-like domains, a short transmembrane domain, and an intracellular region containing a tyrosine kinase domain, split by a 70-amino-acid insert. There are five tyrosine residues that act as major phosphorylation sites (Tyr951, Tyr1054, Tyr1059, Tyr1175 and Tyr1214). For example, binding of PLC-γ to pTyr1175 results in the hydrolysis of PIP2, generating the second messengers DAG and IP3. Binding of VRAP/TSAd to pTyr951 results in the formation of a complex with Src. Binding of Nck to pTyr1214 results in the activation of Cdc42 and p38 MAPK. The binding of adaptor protein Shb to pTyr1175 regulates activation of FAK and PI3K. ^[1]
The crystal structure reveals that Axitinib binds to non-phosphorylated VEGFR2 catalytic domain containing the juxtamembrane (JM) domain. Within the ATP binding site, the heterocycle of Axitinib orients an H-bond acceptor to the backbone donor, as well as a polarized C-H interaction with flanking backbone carbonyls. The head group amide substituent of Axitinib reaches to the JM, forming one direct H-bond to the key pivot point NH backbone of Asp1046 and a second direct H-bond to the carboxylate side chain of Glu885. Besides, one heavy atom extends past the last H-bond into the regulator domain pocket (RDP) within van der Waals distance of the JM Ile804. The inhibitor-protein interactions make the head group fully complement the full length of the channel, and thus increase the affinity with polar charge stabilization as well as hydrophobic interactions. ^[2]
References
[1] Holmes K, et al. Cell Signal. 2007, 19(10), 2003-2012.
[2] McTigue M, et al. Proc Natl Acad Sci U S A. 2012, 109(45), 18281-18289.

Cat.No.	Product Name	Solubility (25°C)
S1040	Sorafenib (Nexavar)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1042	Sunitinib Malate (Sutent)	<1 mg/mL	15 mg/mL	<1 mg/mL
S1490	Ponatinib (AP24534)	<1 mg/mL	30 mg/mL	<1 mg/mL
S1178	Regorafenib (BAY 73-4506)	<1 mg/mL	97 mg/mL	<1 mg/mL
S1119	XL-184 free base (Cabozantinib)	<1 mg/mL	100 mg/mL	<1 mg/mL
S1010	BIBF1120 (Vargatef)	<1 mg/mL	6 mg/mL	3 mg/mL
S1046	Vandetanib (Zactima)	<1 mg/mL	4 mg/mL	<1 mg/mL
S1035	Pazopanib HCl	<1 mg/mL	17 mg/mL	<1 mg/mL
S1005	Axitinib	<1 mg/mL	1 mg/mL	<1 mg/mL
S1264	PD173074	<1 mg/mL	105 mg/mL	105 mg/mL
S1111	Foretinib (GSK1363089, XL880)	<1 mg/mL	127 mg/mL	<1 mg/mL
S1018	Dovitinib (TKI-258)	<1 mg/mL	30 mg/mL	<1 mg/mL
S1017	Cediranib (AZD2171)	<1 mg/mL	90 mg/mL	<1 mg/mL
S2161	RAF265 (CHIR-265)	<1 mg/mL	104 mg/mL	33 mg/mL
S1207	Tivozanib (AV-951)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1470	TSU-68 (SU6668)	<1 mg/mL	62 mg/mL	<1 mg/mL
S1084	Brivanib (BMS-540215)	<1 mg/mL	74 mg/mL	3 mg/mL
S1164	E7080 (Lenvatinib)	<1 mg/mL	40 mg/mL	<1 mg/mL
S1003	Linifanib (ABT-869)	<1 mg/mL	75 mg/mL	<1 mg/mL
S1101	Vatalanib 2HCl (PTK787)	10 mg/mL	85 mg/mL	6 mg/mL
S1361	MGCD-265	<1 mg/mL	104 mg/mL	<1 mg/mL
S2842	SAR131675	<1 mg/mL	30 mg/mL	<1 mg/mL
S1032	Motesanib Diphosphate (AMG-706)	114 mg/mL	114 mg/mL	<1 mg/mL
S2202	NVP-BHG712	<1 mg/mL	101 mg/mL	3 mg/mL
S2769	Dovitinib Dilactic acid (TKI258 Dilactic acid)	70 mg/mL	90 mg/mL	<1 mg/mL
S1181	ENMD-2076	1 mg/mL	105 mg/mL	<1 mg/mL
S2859	Golvatinib (E7050)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1171	CYC116	<1 mg/mL	24 mg/mL	<1 mg/mL
S1220	OSI-930	<1 mg/mL	89 mg/mL	3 mg/mL
S1363	Ki8751	<1 mg/mL	47 mg/mL	<1 mg/mL
S2231	Telatinib (BAY 57-9352)	<1 mg/mL	82 mg/mL	1 mg/mL
S1138	Brivanib alaninate (BMS-582664)	<1 mg/mL	88 mg/mL	88 mg/mL
S1486	AEE788 (NVP-AEE788)	<1 mg/mL	88 mg/mL	<1 mg/mL
S1557	KRN 633	<1 mg/mL	9 mg/mL	<1 mg/mL
S2221	Apatinib (YN968D1)	<1 mg/mL	22 mg/mL	<1 mg/mL
S2896	ZM 323881 HCl	<1 mg/mL	10 mg/mL	<1 mg/mL
S2201	BMS 794833	<1 mg/mL	94 mg/mL	<1 mg/mL
S2200	Raf265 derivative	<1 mg/mL	101 mg/mL	101 mg/mL
S2845	Semaxanib (SU5416)	<1 mg/mL	22 mg/mL	2 mg/mL
S2897	ZM 306416	<1 mg/mL	67 mg/mL	<1 mg/mL
S4001	Cabozantinib malate	<1 mg/mL	127 mg/mL	<1 mg/mL

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	Axitinib (AG-013736) 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.
Clinical Trials	Axitinib is currently in Phase III clinical trial in advanced hepatocellular carcinoma.
Features	Axitinib is superior as second-line therapy compared with sorafenib, the 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.

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).
Formulation	0.5% carboxymethylcellulose (CMC)
Dosages	10, 30 or 100 mg/kg
Administration	Oral daily

References

Chemical Information

Download Axitinib SDF

Molecular Weight (MW)	386.47
Formula	C₂₂H₁₈N₄OS
CAS No.	319460-85-0
Synonyms	AG 013736

Solubility (25°C) DMSO 1 mg/mL Water <1 mg/mL Ethanol <1 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name

Molarity Calculator Dilution Calculator Molecular Weight Calculator

Research Area

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.

Click to enlarge

Rating

Source

J Biomol Screen , 2011, 16, 141-154. Axitinib purchased from Selleck

Method

Western blot, Multiplexing VimPro-Fluc-MDA-MB-231 spheroid viability

Cell Lines

MDA-MB-231 cells

Concentrations

0-100 µM

Incubation Time

Results

When Vimpro-Fluc activity is downregulated between 50% and 70%, there is significant downregulation of vimentin protein expression. When Vimpro-Fluc downregulation reaches ≥70%, then downregulation of vimentin protein expression is more pronounced. of the modulators tested-U0126, dasatinib, axitinib, and pF2341066-all downregulated Vimpro-Fluc activity by≥70%, which correlated with a significant down-reglation of vimentin protein expression. Finally, dose-response curves were generated with both U0126 (IC50 = 2.5 µM) and axitinib (IC50 = 0.25 µM), demonstrating that these small molecules modulate Vimpro-Fluc activity in a dose-dependent manner, indicating that their respective target(s) and signaling pathways play a significant role in maintaining vimentin expression and possibly mesenchymal homeostasis (Fig. B).

Click to enlarge

Rating

Source

Dr Cheri Pasch of UW Madison. Axitinib purchased from Selleck

Method

Western blot

Cell Lines

HUVEC cells

Concentrations

0.1-10 nM

Incubation Time

Results

Axitinib treatment blocks VEGFR2 phosphorylation.

Click to enlarge

Rating

Source

J Biomol Screen , 2011, 16, 141-154. Axitinib purchased from Selleck

Method

Secondary assay

Cell Lines

MDA-MB-231 cells

Concentrations

10 µM

Incubation Time

Results

U0126, pF2341066, axitinib, and pKC412 caused significant inhibition of the invasive potential of Mda-Mb-231 spheroids. Conversely, dasatinib, a potent inhibitor of vimentin gene expression, did not significantly alter the invasive potential of MDA-MB-231 spheroids.

Product Citations (5)

Metformin accelerates the growth of BRAF V600E-driven melanoma by upregulating VEGF-A. [Martin MJ, et al. Cancer Discov 2012;2(4), 344-355]
PubMed: 22576211
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
Axitinib Targeted Cancer Stemlike Cells to Enhance Efficacy of Chemotherapeutic Drugs via Inhibiting the Drug Transport Function of ABCG2. [Wang F, et al. Mol Med 2012;18:887-98]
PubMed: 22549112

Changes in blood vessel maturation in the fibrous cap of the tumor rim. [Naito H, et al. Cancer Sci 2012;103(3):433-8]
PubMed: 22098620
3D models of epithelial-mesenchymal transition in breast cancer metastasis: high-throughput screening assay development,validation, and pilot screen. [Li Q, et al. J Biomol Screen 2011;16(2), 141-154]
PubMed: 21297102

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Related VEGFR Inhibitors

Linifanib (ABT-869)

Linifanib (ABT-869) is a novel, potent ATP-competitive RTK inhibitor for KDR, CSF-1R, Flt-1, Flt-3 and PDGFRβ with IC50 of 4 nM, 3 nM, 3 nM, 3 nM, and 66 nM respectively.
BIBF1120 (Vargatef)

BIBF1120 (Vargatef) is a potent inhibitor of VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50 of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
Cediranib (AZD2171)

Cediranib (AZD2171) is a highly potent VEGFR2 inhibitor with IC50 of 0.5 nM, also inhibits Flt1/4 with IC50 of 5 nM/≤3 nM.
Dovitinib (TKI-258)

Dovitinib (TKI258, CHIR258) is a novel multi-target inhibitor for Flt3, c-Kit, FGFR1/3, VEGFR1/2/3, PDGFRα/β with IC50 of 1 nM, 2 nM, 8 nM/9 nM and 10 nM/13 nM/8 nM, 210 nM/27 nM respectively.
Motesanib Diphosphate (AMG-706)
Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3, PDGFR, c-Kit and Ret with IC50 of 2 nM/3 nM/6 nM, 84 nM, 8 nM and 59 nM, respectively.
Masitinib (AB1010)
Masitinib is a novel tyrosine kinases inhibitor for Kit and PDGFRα/β with IC50 of 200 nM and 540 nM/800 nM, resectively.
Brivanib (BMS-540215)

Brivanib is an ATP-competitive inhibitor against human VEGFR2 and FGFR with IC50 of 25 nM and 148 nM, respectively.
Vatalanib 2HCl (PTK787)

Vatalanib (PTK787) is an inhibitor of VEGFR2/KDR, Flt-1 and c-Kit with IC50 of 37 nM, 77 nM and 730 nM, respectively.
Foretinib (GSK1363089, XL880)

XL880 (GSK1363089, EXEL-2880) is an ATP-competitive inhibitor of MET and KDR with IC50 of 0.4 nM and 0.9 nM, respectively.
Brivanib alaninate (BMS-582664)

BMS-582664 is an oral VEGFR/FGFR inhibitor for VEGFR2, Flk1, VEGFR1 and FGFR1 with IC50 of 25 nM, 89 nM, 380 nM and 148 nM, respectively.

RTKs and Angiogenesis Related Products

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Axitinib + Vandetanib	Vandetanib suppresses proliferation of MTC-TT and TPC-1 cells with IC50 of 0.47 μM and 0.41 μM, respectively, while Axitinib has IC50 of 1.56 μM and 1.14 μM. ^[4]
Axitinib + Sunitinib-Malate-(Sutent)	Sunitinib suppresses proliferation of MTC-TT and TPC-1 cells with IC50 of 0.78 μM and 0.37 μM, respectively, while Axitinib has IC50 of 1.56 μM and 1.14 μM. ^[4]

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Axitinib Licensed by Pfizer