453562-69-1
基本信息
莫特塞尼
莫特沙芬
莫桑尼布雜質(zhì)
莫替沙尼、莫替沙尼
莫特塞尼,莫替沙尼
VEGFR1/VEGFR2/VEGFR3抑制劑(MOTESANIB)
N-(2,3-二氫-3,3-二甲基-1H-吲哚-6-基)-2-[(4-吡啶甲基)氨基]-3-吡啶甲酰胺
3-吡啶甲酰胺, N-(2,3-二氫-3,3-二甲基-1H-吲哚-6-基)-2-[(4-吡啶基甲基)氨基]-
CS-1108
motesanib
Motesanib Base
AMG 706
AMG-706
AMG-706(Motesanib)
Motesanib (AMG-706) Base)
N-(3,3-dimethylindolin-6-yl)-2-(pyridin-4-ylmethylamino)nicotinamide
N-(3,3-dimethylindolin-6-yl)-2-(pyridin-4-ylmethylamino)nicotinamide,AMG706
N-(3,3-diMethylindolin-6-yl){2-[(4-pyridylMethyl)-aMino](3-pyridyl)}-carboxaMide
物理化學(xué)性質(zhì)
常見問題列表
莫特塞尼,也稱為AMG-706,是一種多激酶抑制劑,可選擇性靶向VEGF受體,血小板源性生長(zhǎng)因子受體(PDGFRs)和Kit受體,IC??值分別為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誘導(dǎo)了異種腫瘤的消退。
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 |
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.
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.