Motesanib Diphosphate (AMG 706 Diphosphate) is a potent ATP-competitive inhibitor of VEGFR1/2/3 with IC₅₀s of 2 nM/3 nM/6 nM, respectively, and has similar activity against Kit, and is approximately 10-fold more selective for VEGFR than PDGFR and Ret.

Motesanib Diphosphate (AMG 706 Diphosphate) has broad activity against the human VEGFR family, and displays over 1000-fold selectivity against EGFR, Src, and p38 kinase.Motesanib Diphosphate (AMG 706 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 (AMG 706 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]. Although displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate (AMG 706 Diphosphate) treatment significantly sensitizes the cells to fractionated radiation^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Motesanib Diphosphate (AMG 706 Diphosphate) (100 mg/kg) significantly inhibits VEGF-induced vascular permeability in a time-dependent manner. Oral administration of Motesanib 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 (AMG 706 Diphosphate) induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells^[1]. Motesanib Diphosphate (AMG 706 Diphosphate) in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models^[2]. Motesanib Diphosphate (AMG 706 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

569.44

C₂₂H₂₉N₅O₉P₂

857876-30-3

二磷酸莫替沙尼

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

DMSO : ≥ 110 mg/mL (193.17 mM)

H₂O : 5 mg/mL (8.78 mM; ultrasonic and warming and heat to 60°C)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 25 mg/mL (43.90 mM); Clear solution

  此方案可获得 ≥ 25 mg/mL (43.90 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 250.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• 2.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (4.39 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.39 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (4.39 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (4.39 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [1]. Polverino A, et al. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 2006 Sep 1;66(17):8715-21.

  [2]. Kruser TJ, et al. Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors. Clin Cancer Res, 2010, 16(14), 3639-3647.

  [3]. Coxon A, et al. Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors. Clin Cancer Res, 2009, 15(1), 110-118.

Optimal enzyme, ATP, and substrate (gastrin peptide) concentrations are established for each enzyme using homogeneous time-resolved fluorescence (HTRF) assays. Motesanib 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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cells are preincubated for 2 hours with different concentrations of Motesanib, 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.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

A431 cells are cultured in DMEM (low glucose) with 10% FBS and penicillin/streptomycin/glutamine. Cells are harvested by trypsinization, washed, and adjusted to a concentration of 5×10⁷/mL in serum-free medium. Animals are challenged s.c. with 1×10⁷ cells in 0.2 mL over the left flank. Approximately 10 days thereafter, mice are randomized based on initial tumor volume measurements and treated with either vehicle (Ora-Plus) or Motesanib. Tumor volumes and body weights are recorded twice weekly and/or on the day of sacrifice. Tumor volume is measured with a Pro-Max electronic digital caliper and calculated using the formula length (mm)×width (mm)×height (mm) and expressed in mm³. Data are expressed as mean±SE. Repeated measures ANOVA followed by Scheffe post hoc testing for multiple comparisons is used to evaluate the statistical significance of observed differences^[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Polverino A, et al. AMG 706, an oral, multikinase inhibitor that selectively targets vascular endothelial growth factor, platelet-derived growth factor, and kit receptors, potently inhibits angiogenesis and induces regression in tumor xenografts. Cancer Res. 2006 Sep 1;66(17):8715-21.

  [2]. Kruser TJ, et al. Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors. Clin Cancer Res, 2010, 16(14), 3639-3647.

  [3]. Coxon A, et al. Broad antitumor activity in breast cancer xenografts by motesanib, a highly selective, oral inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and Kit receptors. Clin Cancer Res, 2009, 15(1), 110-118.