生物活性

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. Althouth displaying little antiproliferative activity on cell growth of HUVECs alone, Motesanib Diphosphate treatment significantly sensitizes the cells to fractionated radiation. 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.

化学数据

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的K_m系数（3），再除以大鼠的K_m系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。

储备液配制

以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。