莫特塞尼
中文名称:
莫特塞尼
中文同义词:
莫特沙芬;莫特塞尼,莫替沙尼;莫替沙尼、莫替沙尼;3-吡啶甲酰胺, N-(2,3-二氢-3,3-二甲基-1H-吲哚-6-基)-2-[(4-吡啶基甲基)氨基]-;莫桑尼布杂质;VEGFR1/VEGFR2/VEGFR3抑制剂(MOTESANIB);N-(2,3-二氢-3,3-二甲基-1H-吲哚-6-基)-2-[(4-吡啶甲基)氨基]-3-吡啶甲酰胺;莫特塞尼
英文名称:
Motesanib
英文同义词:
CS-1108;AMG 706; AMG-706;N-(3,3-diMethylindolin-6-yl){2-[(4-pyridylMethyl)-aMino](3-pyridyl)}-carboxaMide;3-PyridinecarboxaMide, N-(2,3-dihydro-3,3-diMethyl-1H-indol-6-yl)-2-[(4-pyridinylMethyl)aMino]-;Motesanib Base;AMG-706(Motesanib);Motesanib (AMG-706) Base);motesanib
CAS号:
453562-69-1
分子式:
C22H23N5O
分子量:
373.45
EINECS号:
相关类别:
科研试剂;细胞生物学试剂;信号转导通路激酶抑制剂;小分子抑制剂;小分子抑制剂，天然产物;蛋白酪氨酸激酶;API;Antineoplastic;Inhibitors
Mol文件:
453562-69-1.mol
沸点
517.3±50.0 °C(Predicted)
密度
1.251
形态
White powder solid.
酸度系数(pKa)
11.75±0.40(Predicted)
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
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.
