Axitinib (AG 013736)

Licensed by Pfizer Catalog No.S1005

For research use only.

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 in Porcine aorta endothelial cells, respectively.

Axitinib (AG 013736) Chemical Structure

CAS No. 319460-85-0

Selleck's Axitinib (AG 013736) has been cited by 121 publications

Purity & Quality Control

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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 in Porcine aorta endothelial cells, respectively.
Features Superior as second-line therapy relative to sorafenib (current standard-of-care).
Targets
VEGFR1/FLT1 [1]
(Porcine aorta endothelial cells)
VEGFR2/Flk1 [1]
(Porcine aorta endothelial cells)
VEGFR2/KDR [1]
(Porcine aorta endothelial cells)
VEGFR3 [1]
(Porcine aorta endothelial cells)
PDGFRβ [1]
(Porcine aorta endothelial cells)
Click to View More Targets
0.1 nM 0.18 nM 0.2 nM 0.1 nM-0.3 nM 1.6 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
EoL-1-cell MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnv1TWM2OD1yLkCwNFA2OTNizszN Mnz5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI5QTl{Nj:nQnNCVkeHUkyvZV4>
NCI-H1703 M3jjbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M361WWlEPTB;MD6wNFA6ODJizszN M2fKNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzQDl7Mk[vK|5USU6JRWK8M4E,
KASUMI-1 NVfjVGpLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1G5TmlEPTB;MD6wNFY5OiEQvF2= NYL1N4ltRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ6OUmyOk8oRlODTlfFVlww[T5?
CGTH-W-1 MmK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LGSmlEPTB;MD6wNFczOiEQvF2= MmTLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVI5QTl{Nj:nQnNCVkeHUkyvZV4>
A204 NWH0coZtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHpTWM2OD1yLkCwPVkzKM7:TR?= M{jkS|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzQDl7Mk[vK|5USU6JRWK8M4E,
HOP-62 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHH6VJBKSzVyPUCuNVA5OzZizszN NIjUbIM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOjh7OUK2M{c,W0GQR1XSQE9iRg>?
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KU812 MkLCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX3EPIZ{UUN3ME2wMlE3PTd5IN88US=> M2rETFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzQDl7Mk[vK|5USU6JRWK8M4E,
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MEG-01 NUHPN2J7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmnjTWM2OD1yLkSyN|YyKM7:TR?= NYTuVlJ4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ6OUmyOk8oRlODTlfFVlww[T5?
MFM-223 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEHVXJVKSzVyPUCuOFQ4PzZizszN M4G4NlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzQDl7Mk[vK|5USU6JRWK8M4E,
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NEC8 NVrH[mVxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfSTWM2OD1yLkeyNVE{KM7:TR?= M2nzN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEzQDl7Mk[vK|5USU6JRWK8M4E,
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Rh18 M1:1RpFJXFNiYYPzZZk> MV7xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? Mo\1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
HUVEC M1njU2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 M3;VfFEhcHJ? NEDjOW5CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JHZGT0Zvc4TpcZVt[XSnZDDIWXZGSyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCC4aXHibYxqfHlicILlbY5kfWKjdHXkJIZweiBzIHjyJIZwdGyxd3XkJIJ6KGGmZHn0bY9vKG:oIG\FS2YhdWWjc4Xy[YQh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODByNTFOwG0v NWe0eWJtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ6OUmyOk8oRkOqRV3CUFww[T5?
HUVEC NWOwN4JuSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M{C4[|EhcHJ? M{nTTmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgWmVITi2|dHnteYxifGWmIFjVWmVEKGOnbHzzJIF{e2W|c3XkJIF{KHKnZIXjeIlwdiCrbjDj[YxtKH[rYXLpcIl1gSCycnXpcoN2[mG2ZXSg[o9zKDFiaIKg[o9tdG:5ZXSgZpkh[WSmaYTpc44hd2ZiVlXHSkBu\WG|dYLl[EBi\nSncjC3NkBpenNiaX6gdJJme2WwY3Wgc4Yh[WykdX3pckBjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCwNlch|ryPLh?= NU\3cFlXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTJ6OUmyOk8oRkOqRV3CUFww[T5?
A549 M{HMfGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MlvtOFghcHK| Ml\SRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDWSWdHNXO2aX31cIF1\WRiaIXtZY4hSTV2OTDj[YxteyCjZoTldkA1QCCqcoOgZpkhS0ONODDhd5NigSxiSVO1NEA:KDJ{LkSg{txONg>? MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlg6QTJ4Lze+R4hGVUKOPD;hQi=>
HepG2 M{jSfGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MlTMOFghcHK| M1:5emFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgWmVITi2|dHnteYxifGWmIHj1cYFvKEincFeyJINmdGy|IHHmeIVzKDR6IHjyd{BjgSCFQ1u4JIF{e2G7LDDJR|UxKD1iM{iuO{DPxE1w MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNlg6QTJ4Lze+R4hGVUKOPD;hQi=>
Assay
Methods Test Index PMID
Western blot p-c-kit / c-kit / p-AKT / AKT / p-ERK / ERK / p-STAT3 / STAT3 / p-STAT5 / STAT5 / p-S6K / S6K / p-S6 / S6 ; PARP / cleaved PARP / caspase-3 / cleaved caspase-3 31205508
Immunofluorescence alpha-tubulin 26474283
Growth inhibition assay Cell viability 26474283
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.

Protocol (from 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 Research:

[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.

  • (Only for Reference)
Animal Research:

[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
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 35 mg/mL warmed
(90.56 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 386.47
Formula

C22H18N4OS

CAS No. 319460-85-0
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CNC(=O)C1=CC=CC=C1SC2=CC3=C(C=C2)C(=NN3)C=CC4=CC=CC=N4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04941768 Recruiting -- Carcinoma Renal Cell Merck Healthcare KGaA Darmstadt Germany an affiliate of Merck KGaA Darmstadt Germany|Merck Serono GmbH an affiliate of Merck KGaA Darmstadt Germany August 9 2021 --
NCT04682587 Active not recruiting Drug: Axitinib|Drug: Avelumab|Drug: Pembrolizumab Renal Cell Carcinoma Pfizer February 24 2021 --
NCT04669366 Recruiting Drug: sunitinib|Drug: axitinib Kidney Neoplasms Pfizer January 20 2021 --
NCT04626128 Recruiting Drug: CLS-AX|Drug: Anti-VEGF Neovascular Age-related Macular Degeneration Clearside Biomedical Inc. December 15 2020 Phase 1|Phase 2
NCT04637204 Completed Drug: Cabozantinib|Drug: Axitinib Renal Cell Carcinoma Ipsen November 24 2020 --

(data from https://clinicaltrials.gov, updated on 2021-09-06)

Tech Support

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

Tel: +1-832-582-8158 Ext:3
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Frequently Asked Questions

Question 1:
We would like to store at -80℃ after it dissolved in CMC. Do you have any infomation about the suggested concentration in CMC?

Answer:
Axitinib in 0.5% CMC at up to 30mg/ml is a suspension for oral gavage administration only. We don't suggest customer to freeze down the solution but to make fresh if possible. Customer can store it for 1-2 weeks at 4 degree for continuous use.

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