莫特塞尼

简介用途用途生物活性靶点体外研究体内研究莫特塞尼试剂级价格

莫特塞尼

CAS号:453562-69-1
英文名:Motesanib
中文名:莫特塞尼
CBNumber:CB01518524
分子式:C22H23N5O
分子量:373.45
MOL File:453562-69-1.mol

莫特塞尼化学性质

熔点 :147-150°C
沸点 :517.3±50.0 °C(Predicted)
密度 :1.251
储存条件 :Refrigerator
溶解度 :DMSO (Slightly), Methanol (Slightly)
形态 :White powder solid.
酸度系数(pKa) :11.75±0.40(Predicted)
颜色 :Pale Yellow

安全信息

海关编码 :2933399990

莫特塞尼性质、用途与生产工艺

简介 Motesanib 是一种有效的 VEGFR1/2/3 的 ATP 竞争性抑制剂，IC50 值为 2 nM/3 nM/6 nM，与对Kit的选择性相似，是 PDGFR 和 Ret的 10 倍多。
用途
莫特塞尼，也称为AMG-706，是一种多激酶抑制剂，可选择性靶向VEGF受体，血小板源性生长因子受体（PDGFRs）和Kit受体，IC₅₀值分别为2 nM（VEGFR1），3 nM（VEGFR2），6 nM （VEGFR3），84 nM（PDGFR）和8 nM（Kit）。它也有效地抑制了血管生成并诱导了异种肿瘤的消退。
用途莫特塞尼是一种Flk-1、Flt-4、PDGFR-和c-Kit的抑制剂。
生物活性 Motesanib (AMG-706)是一种具有口服生物活性的受体酪氨酸激酶 (receptor tyrosine kinase)抑制剂，对VEGFR1, VEGFR2, VEGFR3, Kit, PDGFR和Ret的IC50值分别为2、3、6、8、84和59 nM。
靶点
Target Value
VEGFR1
(Cell-free assay) 2 nM
VEGFR2
(Cell-free assay) 3 nM
VEGFR3
(Cell-free assay) 6 nM
c-Kit
(Cell-free assay) 8 nM
c-Kit
(Cell-free assay) 8 nM
体外研究

Motesanib has broad activity against the human VEGFR family, and displays > 1000 selectivity against EGFR, Src, and p38 kinase. Motesanib significantly inhibits VEGF-induced cellular proliferation of HUVECs with an IC ₅₀ of 10 nM, while displaying little effect at bFGF-induced proliferation with an IC ₅₀ of >3,000 nM. Motesanib also potently inhibits PDGF-induced proliferation and SCF-induced c-kit phosphorylation with IC ₅₀ 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 treatment significantly sensitizes the cells to fractionated radiation.
体内研究

Motesanib (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 ED ₅₀ of 2.1 mg/kg and 4.9 mg/kg, respectively. Motesanib induces a dose-dependent tumor regression of established A431 xenografts by selectively targeting neovascularization in tumor cells. Motesanib in combination with radiation displays significant anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) xenograft models. Motesanib 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.