Home Protein Tyrosine Kinase VEGFR inhibitor - PDGFR inhibitor - c-Kit inhibitor Motesanib Diphosphate (AMG-706) For research use only.

Motesanib Diphosphate (AMG-706)

Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit (c-Kit), ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3.

Motesanib Diphosphate (AMG-706) Chemical Structure

Motesanib Diphosphate (AMG-706) Chemical Structure

CAS No. 857876-30-3

Purity & Quality Control

Motesanib Diphosphate (AMG-706) Related Products

Signaling Pathway

VEGFR Signaling Pathways

VEGFR Signaling Pathway

Biological Activity

Description Motesanib Diphosphate (AMG-706) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; similar activity against Kit (c-Kit), ~10-fold more selective for VEGFR than PDGFR and Ret. Phase 3.
Targets
VEGFR1 [1]
(Cell-free assay)		 VEGFR2 [1]
(Cell-free assay)		 VEGFR2/Flk1 [1]
(Cell-free assay)		 VEGFR3 [1]
(Cell-free assay)		 Kit [1]
(Cell-free assay)		 Click to View More Targets
2 nM 3 nM 6 nM 6 nM 8 nM
In vitro
In vitro

Motesanib Diphosphate has broad activity against the human VEGFR family, and displays >1000 selectivity against EGFR, Src, and p38 kinase. Motesanib Diphosphate significantly inhibits VEGF-induced cellular proliferation of HUVECs with an IC50 of 10 nM, while displaying little effect at bFGF-induced proliferation with an IC50 of >3,000 nM. Motesanib Diphosphate also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with IC50 of 207 nM and 37 nM, respectively, but not effective against the EGF-induced EGFR phosphorylation and cell viability of A431 cells. [1] Althouth displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate treatment significantly sensitizes the cells to fractionated radiation. [2]
Kinase Assay In vitro kinase assays
Optimal enzyme, ATP, and substrate (gastrin peptide) concentrations are established for each enzyme using homogeneous time-resolved fluorescence (HTRF) assays. Motesanib Diphosphate is tested in a 10-point dose-response curve for each enzyme using an ATP concentration of two-thirds Km for each. Most assays consist of enzyme mixed with kinase reaction buffer [20 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 5 mM MnCl2, 100 mM NaCl, 1.5 mM EGTA]. A final concentration of 1 mM DTT, 0.2 mM NaVO4, and 20 μg/mL BSA is added before each assay. For all assays, 5.75 mg/mL streptavidin-allophycocyanin and 0.1125 nM Eu-PT66 are added immediately before the HTRF reaction. Plates are incubated for 30 minutes at room temperature and read on a Discovery instrument. IC50 values are calculated using the Levenberg-Marquardt algorithm into a four-parameter logistic equation.
Cell Research Cell lines A431, MO7e, HUVEC and NHDF cells
Concentrations Dissolved in DMSO, final concentrations ~25 μM
Incubation Time 2 hours
Method

Cells are preincubated for 2 hours with different concentrations of Motesanib Diphosphate, and exposed with 50 ng/mL VEGF or 20 ng/mL bFGF for an additional 72 hours. Cells are washed twice with DPBS, and plates are frozen at -70 °C for 24 hours. Proliferation is assessed by the addition of CyQuant dye, and plates are read on a Victor 1420 workstation. IC50 data are calculated using the Levenberg-Marquardt algorithm into a four-parameter logistic equatio
In Vivo
In vivo

Administration of Motesanib Diphosphate at 100 mg/kg significantly inhibits VEGF-induced vascular permeability in a time-dependent manner. Oral administration of Motesanib Diphosphate twice daily or once daily potently inhibits, in a dose-dependent manner, VEGF-induced angiogenesis using the rat corneal model with ED50 of 2.1 mg/kg and 4.9 mg/kg, respectively. Motesanib Diphosphate induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells. [1] Administration of Motesanib Diphosphate in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. [2] Motesanib Diphosphate treatment also induces significant dose-dependent reductions in tumor growth and blood vessel density of MCF-7, MDA-MB-231, or Cal-51 xenografts. [3]
Animal Research Animal Models Female Sprague-Dawley rats with induced corneal angiogenesis, and female CD-1 nu/nu mice injected s.c. with A431 cells
Dosages ~100 mg/kg
Administration Orally administered twice daily or once daily
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01386866 Completed
Advanced Solid Tumors
Amgen
 May 2009 Phase 1
NCT00448786 Completed
Solid Tumors
Amgen
 February 2007 Phase 1
NCT00322400 Completed
Locally Recurrent and Metastatic Breast Cancer
Amgen
 March 2006 Phase 1
NCT01235416 Completed
Histologically or Cytologically Documented Solid Tumors
Amgen
 September 2005 Phase 1

Chemical Information & Solubility

Molecular Weight 569.44 Formula

C22H23N5O.2H3PO4
CAS No. 857876-30-3 SDF Download Motesanib Diphosphate (AMG-706) SDF
Smiles CC1(CNC2=C1C=CC(=C2)NC(=O)C3=C(N=CC=C3)NCC4=CC=NC=C4)C.OP(=O)(O)O.OP(=O)(O)O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (175.61 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : 19 mg/mL

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

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.

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
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Motesanib Diphosphate (AMG-706) | Motesanib Diphosphate (AMG-706) supplier | purchase Motesanib Diphosphate (AMG-706) | Motesanib Diphosphate (AMG-706) cost | Motesanib Diphosphate (AMG-706) manufacturer | order Motesanib Diphosphate (AMG-706) | Motesanib Diphosphate (AMG-706) distributor