中文名称:

SU-14813

中文同义词:

5-[(5-氟-1,2-二氢-2-氧代-3H-吲哚-3-亚基)甲基]-N-[(2S)-2-羟基-3-(4-吗啉基)丙基]-2,4-二甲基-1H-吡咯-3-甲酰胺;SU-14813游离态;受体酪氨酸激酶抑制剂(SU14813);5-[(5-氟-1,2-二氢-2-氧代-3H-吲哚-3-亚烷基)甲基]-N-[(2S)-2-羟基-3-(4-吗啉基)丙基]-2,4-二甲基-1H-吡咯-3-甲酰胺;5-((5-氟-2-氧代吲哚-3-亚基)甲基)-N-(2-羟基-3-吗啉代丙基)-2,4-二甲基-1H-吡咯-3-甲酰胺

英文名称:

SU14813

英文同义词:

SU14813;5-[(5-Fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-(4-morpholinyl)propyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide;CS-1149;SU14813(Random Configuration);SU-14813; SU 14813;5-[(Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N- [ 2-hydroxy-3-(4-morpholinyl)propyl]-2,4-dimethyl-1H-pyrrole-3-carb;1H-Pyrrole-3-carboxamide, 5-[(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-(4-morpholinyl)propyl]-2,4-dimethyl-

CAS号:

627908-92-3

分子式:

C23H27FN4O4

分子量:

442.48

EINECS号:

相关类别:

细胞生物学试剂;抑制剂;蛋白酪氨酸激酶

Mol文件:

627908-92-3.mol

沸点 

685.6±55.0 °C(Predicted)

密度 

1.341

酸度系数(pKa)

11.24±0.20(Predicted)

生物活性

SU14813 (SU 014813)是一种多受体 tyrosine kinase 的抑制剂，对于 VEGFR2、VEGFR1、PDGFRβ 和 Kit (c-Kit) 的IC50值分别为50 nM，2 nM，4 nM和15 nM。SU14813 具有强大的抗血管生成和抗肿瘤活性。

靶点

Target Value VEGFR1 (Cell-free assay) 2 nM PDGFRβ (Cell-free assay) 4 nM KIT (Cell-free assay) 15 nM VEGFR2 (Cell-free assay) 50 nM

Target

Value

VEGFR1 (Cell-free assay)

2 nM

PDGFRβ (Cell-free assay)

4 nM

KIT (Cell-free assay)

15 nM

VEGFR2 (Cell-free assay)

50 nM

体外研究

SU14813 inhibits ligand-dependent and ligand-independent proliferation, migration, and survival of endothelial cells and/or tumor cells expressing these targets. SU14813 inhibits cellular ligand-dependent phosphorylation of VEGFR-2 (transfected NIH 3T3 cells), PDGFR-β (transfected NIH 3T3 cells), KIT (Mo7e cells), and FLT3-internal tandem duplication (FLT3-ITD; MV4;11 cells) as well as FMS/CSF1R (transfected NIH 3T3 cells). SU14813 inhibits VEGFR-2, PDGFR-β, and KIT phosphorylation in porcine aorta endothelial cells overexpressing these targets, with cellular IC 50 values of 5.2, 9.9, and 11.2 nM, respectively. SU14813 inhibits the growth of U-118MG with an IC 50 of 50 to 100 nM.

体内研究

SU14813 inhibits VEGFR-2, PDGFR-β, and FLT3 phosphorylation in xenograft tumors in a dose- and time-dependent fashion. The plasma concentration required for in vivo target inhibition is estimated to be 100 to 200 ng/mL. Used as monotherapy, SU14813 exhibits broad and potent antitumor activity resulting in regression, growth arrest, or substantially reduces growth of various established xenografts derived from human or rat tumor cell lines. Treatment in combination with docetaxel significantly enhances both the inhibition of primary tumor growth and the survival of the tumor-bearing mice compared with administration of either agent alone.