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Motesanib Diphosphate (AMG-706)

Name: Motesanib Diphosphate (AMG-706)
Brand: Selleck Chemicals
SKU: S1032
Rating: 5 (11 reviews)

Catalog No.S1032

For research use only.

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

Selleck's Motesanib Diphosphate (AMG-706) has been cited by 11 Publications

3 Customer Reviews

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VEGFR Signaling Pathway Map

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

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]

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, which can be markedly enhanced when combined with docetaxel or tamoxifen. ^[3]

Protocol (from reference)

Kinase Assay:^[1]	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 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:^[1]	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
Animal Research:^[1]	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

References

Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): Saline For best results, use promptly after mixing.	30 mg/mL

Chemical Information

Molecular Weight	569.44
Formula	C₂₂H₂₃N₅O.2H₃PO₄
CAS No.	857876-30-3
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
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

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01386866	Completed	Drug: AMG 706	Advanced Solid Tumors	Amgen	May 2009	Phase 1
NCT00448786	Completed	Drug: AMG 706	Solid Tumors	Amgen	February 2007	Phase 1
NCT00322400	Completed	Drug: Docetaxel\|Drug: Paclitaxel\|Drug: AMG 706	Locally Recurrent and Metastatic Breast Cancer	Amgen	March 2006	Phase 1
NCT01235416	Completed	Drug: AMG 706	Histologically or Cytologically Documented Solid Tumors	Amgen	September 2005	Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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