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: 857876-30-3

Selleck's Motesanib Diphosphate (AMG-706) has been cited by 12 Publications

3 Customer Reviews

Purity & Quality Control

Batch: Purity: 99.99%
99.99

Motesanib Diphosphate (AMG-706) Related Products

Signaling Pathway

Choose Selective VEGFR Inhibitors

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


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In vivo
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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

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