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Motesanib Diphosphate (AMG-706)

Name: Motesanib Diphosphate (AMG-706)
Brand: Selleck Chemicals
SKU: S1032
Rating: 5 (12 reviews)

Catalog No.S1032 Purity:99.99%

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

CAS No. 857876-30-3

Purity & Quality Control

Batch: Purity: 99.99%

99.99

Motesanib Diphosphate (AMG-706) Related Products

Related Targets	VEGFR1 VEGFR2 VEGFR3	Click to Expand
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Related Compound Libraries	Kinase Inhibitor Library Tyrosine Kinase Inhibitor Library PI3K/Akt Inhibitor Library Cell Cycle compound library Angiogenesis Related compound Library	Click to Expand

Signaling Pathway

VEGFR Signaling Pathway

Biological Activity

Description

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	Click to View More Targets

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
Kinase Assay	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 K_m 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
Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2024-05-22)
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

References

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)	3 years-20°Cpowder	Storage of Stock Solutions Aliquot the stock solutions to avoid repeated freeze-thaw cycles	1 year-80°Cin solvent
Storage (From the date of receipt)	3 years-20°Cpowder		1 month-20°Cin solvent

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
Clear solution	saline	19.000mg/ml (33.37mM)	Taking the 1 mL working solution as an example, add 19 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	Saline Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (52.68mM)	Taking the 1 mL working solution as an example, add 30 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Clear solution	saline	100.000mg/ml (175.61mM)	Taking the 1 mL working solution as an example, add 100 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	saline	19.000mg/ml (33.37mM)	Taking the 1 mL working solution as an example, add 19 mg of this product to 1 ml of physiological saline (0.9% NaCL solution), mix evenly to make it clear, The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

Preparing Stock Solutions

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
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Dilution Calculator Molecular Weight Calculator

In vivo Formulation Calculator (Clear solution)

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

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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
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