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Motesanib Diphosphate

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Chemical Structure| 857876-30-3 同义名 : AMG 706 Diphosphate;AMG 706;Motesanib
CAS号 : 857876-30-3
货号 : A238109
分子式 : C22H29N5O9P2
纯度 : 98%
分子量 : 569.441
MDL号 : MFCD12407403
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(184.39 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 5 mg/mL(8.78 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：

PO 0.5% CMC-Na 40 mg/mL suspension

生物活性
靶点

  • VEGFR1

    VEGFR1, IC50:2 nM

  • VEGFR3

    VEGFR3, IC50:6 nM

  • VEGFR2

    VEGFR2/Flk1, IC50:3 nM

    VEGFR2, IC50:3 nM

  • PDGFR

    PDGFR, IC50:84 nM

  • c-Kit

    Kit, IC50:8 nM
描述 Motesanib diphosphate (AMG 706 Diphosphate) is ATP-competitive inhibitor of VEGFR1, VEGFR2 and VEGFR3 with IC50 of 2 nM, 3 nM and 6 nM, respectively. It also shows better inhibitory activity against c-Kit, PDGFR, and RET. Motesanib 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[3]. Motesanib inhibited VEGF-stimulated HUVEC proliferation in vitro, as well as VEGFR2 kinase activity. Additionally, motesanib and fractionated radiation showed additive inhibitory effects on HUVEC proliferation[4]. Treatment with motesanib alone or in combination with chemotherapy inhibits tumor growth in vivo in various models of human breast cancer[5]. Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.76mL

0.35mL

0.18mL

8.78mL

1.76mL

0.88mL

17.56mL

3.51mL

1.76mL
参考文献

[1]Kruser TJ, Wheeler DL, et al. Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors. Clin Cancer Res. 2010 Jul 15;16(14):3639-47.

[2]Polverino A, Coxon 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.

[3]Polverino A, Coxon A, Starnes C, Diaz Z, DeMelfi T, Wang L, Bready J, Estrada J, Cattley R, Kaufman S, Chen D, Gan Y, Kumar G, Meyer J, Neervannan S, Alva G, Talvenheimo J, Montestruque S, Tasker A, Patel V, Radinsky R, Kendall R. 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

[4]Kruser TJ, Wheeler DL, Armstrong EA, Iida M, Kozak KR, van der Kogel AJ, Bussink J, Coxon A, Polverino A, Harari PM. Augmentation of radiation response by motesanib, a multikinase inhibitor that targets vascular endothelial growth factor receptors. Clin Cancer Res. 2010 Jul 15;16(14):3639-47

[5]Coxon A, Bush T, Saffran D, Kaufman S, Belmontes B, Rex K, Hughes P, Caenepeel S, Rottman JB, Tasker A, Patel V, Kendall R, Radinsky R, Polverino A. 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 Jan 1;15(1):110-8

[6]Sherman SI, Wirth LJ, Droz JP, Hofmann M, Bastholt L, Martins RG, Licitra L, Eschenberg MJ, Sun YN, Juan T, Stepan DE, Schlumberger MJ; Motesanib Thyroid Cancer Study Group. Motesanib diphosphate in progressive differentiated thyroid cancer. N Engl J Med. 2008 Jul 3;359(1):31-42