Motesanib Diphosphate (AMG-706)

製品コードS1032 バッチS103201

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₂H₂₃N₅O.2H₃PO₄

分子量

569.44

CAS No.

857876-30-3

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

100 mg/mL (175.61 mM)

Water (warmed with 50ºC water bath)

100 mg/mL (175.61 mM)

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

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.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Motesanib Diphosphate (AMG-706)は、VEGFR1/2/3の強力なATP競合阻害剤で、IC50はそれぞれ2 nM/3 nM/6 nMです。Kit (c-Kit)に対しても同様の活性を示し、PDGFRおよびRetよりもVEGFRに対して約10倍選択的です。フェーズ3。
in vitro	Motesanib Diphosphate (AMG-706) has broad activity against the human VEGFR family, and displays >1000 selectivity against EGFR, Src, and p38 kinase. It 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. This compound also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with IC50 of 207 nM and 37 nM, respectively, but is 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, it significantly sensitizes the cells to fractionated radiation.
in vivo	Motesanib Diphosphate (AMG-706) administration at 100 mg/kg significantly inhibits VEGF-induced vascular permeability in a time-dependent manner. Oral administration of this compound 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. It induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells. When administered in combination with radiation, it displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. Treatment with this compound also induces significant dose-dependent reductions in tumor growth and blood vessel density of MCF-7, MDA-MB-231, or Cal-51 xenografts.

プロトコル(参考用のみ)

キナーゼアッセイ	In vitro kinase assays
キナーゼアッセイ	Optimal enzyme, ATP, and substrate (gastrin peptide) concentrations are established for each enzyme using homogeneous time-resolved fluorescence (HTRF) assays. For Motesanib Diphosphate (AMG-706), a 10-point dose-response curve is tested 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.
細胞アッセイ	細胞株	A431, MO7e, HUVEC and NHDF cells
	濃度	Dissolved in DMSO, final concentrations ~25 μM
	反応時間	2 hours
	実験の流れ	Cells are preincubated for 2 hours with different concentrations of Motesanib Diphosphate (AMG-706), and exposed with 50 ng/mL VEGF or 20 ng/mL bFGF for an additional 72 hours. After washing twice with DPBS, 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.
動物実験	動物モデル	Female Sprague-Dawley rats with induced corneal angiogenesis, and female CD-1 nu/nu mice injected s.c. with A431 cells
	投薬量	~100 mg/kg
	投与方法	Orally administered twice daily or once daily

参考

https://pubmed.ncbi.nlm.nih.gov/16951187/
https://pubmed.ncbi.nlm.nih.gov/20507929/
https://pubmed.ncbi.nlm.nih.gov/19118038/

カスタマーフィードバック

: Data from [Data independently produced by J Ocul Pharmacol Ther, 2014, 10.1089/jop.2014.0023]

: Data from [Cardiovasc Res, 2011, 91, 402-11]

: Data from [Cardiovasc Res, 2011, 91, 402-11]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Anosmin-1-Like Effect of UMODL1/Olfactorin on the Chemomigration of Mouse GnRH Neurons and Zebrafish Olfactory Axons Development [ Front Cell Dev Biol, 2022, 10:836179]	PubMed: 35223856
Preclinical Evaluation of Ixabepilone in Combination with VEGF Receptor and PARP Inhibitors in Taxane-Sensitive and Taxane-Resistant MDA-MB-231 Breast Cancer Cells [ J Pharm Sci, 2022, 111(8):2180-2190]	PubMed: 35700798
Extension of the Mechanistic Tissue Distribution Model of Rodgers and Rowland by Systematic Incorporation of Lysosomal Trapping: Impact on Unbound Partition Coefficient and Volume of Distribution Predictions in the Rat [ Drug Metab Dispos, 2021, 49(1):53-61]	PubMed: 33148688
Cardiac Reprogramming Factors Synergistically Activate Genome-wide Cardiogenic Stage-Specific Enhancers [ Cell Stem Cell, 2019, 25(1):69-86]	PubMed: 31080136
Targeting the Kaposi Sarcoma Herpesvirus ORF 21 tyrosine kinase and viral lytic reactivation by tyrosine kinase inhibitors approved for clinical use. [ J Virol, 2019, 10.1128/JVI.01791-19]	PubMed: 31826996
[ Cancer Res, 2016, ]	PubMed: 27488524
Dual inhibition of EGFR and MET induces synthetic lethality in triple-negative breast cancer cells through downregulation of ribosomal protein S6 [ Int J Oncol, 2015, 47(1):122-32]	PubMed: 25955731
VEGF/SDF-1 promotes cardiac stem cell mobilization and myocardial repair in the infarcted heart. [Tang JM, et al. Int J Cardiol, 2015, 183C:221-231]	PubMed: 25679991
Antiangiogenic Effects of Topically Administered Multiple Kinase Inhibitor, Motesanib (AMG 706), on Experimental Choroidal Neovascularization in Mice [Rho CR, et al. J Ocul Pharmacol Ther, 2015, 31(1):25-31]
Bioluminescent cell-based NAD(P)/NAD(P)H assays for rapid dinucleotide measurement and inhibitor screening [ Assay Drug Dev Technol, 2014, 12(9-10):514-26]	PubMed: 25506801

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。