product name Motesanib Diphosphate
Description: Motesanib Diphosphate (also known as AMG-706) is a potent ATP-competitive, orally bioavailable inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; it has similar activity against Kit, and ~10-fold more selective for VEGFR than PDGFR and Ret. Motesanib selectively targets and inhibits VEGFR, PDGFR, kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.
References: Cancer Res. 2006;66(17):8715-21; Clin Cancer Res. 2010;16(14):3639-47; Clin Cancer Res. 2009;15(1):110-8.
569.44
Formula
C22H23N5O.2H3PO4
CAS No.
857876-30-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (175.6 mM)
Water: 19 mg/mL (33.4 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Saline: 30 mg/mL
Synonyms
AMG-706
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402042
| In Vitro |
In vitro activity: 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. Althouth displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate treatment significantly sensitizes the cells to fractionated radiation. 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 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 Assay: Cells ( A431, MO7e, HUVEC and NHDF 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 equation. |
|---|---|
| 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. Administration of Motesanib Diphosphate in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. 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. |
| Animal model | Female Sprague-Dawley rats with induced corneal angiogenesis, and female CD-1 nu/nu mice injected s.c. with A431 cells |
| Formulation & Dosage | Dissolved in a suspension in Ora-Plus vehicle adjusted to pH 2.0; 100 mg/kg; oral gavage |
| References | Cancer Res. 2006 Sep 1;66(17):8715-21; Clin Cancer Res. 2010 Jul 15;16(14):3639-47; Clin Cancer Res. 2009 Jan 1;15(1):110-8. |
Related Posts
product name Motesanib Diphosphate
Description: Motesanib Diphosphate (also known as AMG-706) is a potent ATP-competitive, orally bioavailable inhibitor of VEGFR1/2/3 with IC50 of 2 nM/3 nM/6 nM, respectively; it has similar activity against Kit, and ~10-fold more selective for VEGFR than PDGFR and Ret. Motesanib selectively targets and inhibits VEGFR, PDGFR, kit, and Ret receptors, thereby inhibiting angiogenesis and cellular proliferation.
References: Cancer Res. 2006;66(17):8715-21; Clin Cancer Res. 2010;16(14):3639-47; Clin Cancer Res. 2009;15(1):110-8.
569.44
Formula
C22H23N5O.2H3PO4
CAS No.
857876-30-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (175.6 mM)
Water: 19 mg/mL (33.4 mM)
Ethanol: <1 mg/mL
Solubility (In vivo)
Saline: 30 mg/mL
Synonyms
AMG-706
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402042
| In Vitro |
In vitro activity: 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. Althouth displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate treatment significantly sensitizes the cells to fractionated radiation. 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 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 Assay: Cells ( A431, MO7e, HUVEC and NHDF 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 equation. |
|---|---|
| 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. Administration of Motesanib Diphosphate in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. 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. |
| Animal model | Female Sprague-Dawley rats with induced corneal angiogenesis, and female CD-1 nu/nu mice injected s.c. with A431 cells |
| Formulation & Dosage | Dissolved in a suspension in Ora-Plus vehicle adjusted to pH 2.0; 100 mg/kg; oral gavage |
| References | Cancer Res. 2006 Sep 1;66(17):8715-21; Clin Cancer Res. 2010 Jul 15;16(14):3639-47; Clin Cancer Res. 2009 Jan 1;15(1):110-8. |