630124-46-8 | AST 487
英文名称
AST 487
分子式
C26H30F3N7O2
分子量
529.56
结构式
中文别名
英文别名
| 属性 | 值 |
|---|---|
| 密度 | 1.341±0.06 g/cm3(Predicted) |
| 形态 | 固体 |
| 沸点 | 563.1±50.0 °C(Predicted) |
| 熔点 | 162-164°C |
| 颜色 | 白色至浅黄色 |
| 溶解度 | 可溶于DMSO（少许）、甲醇（少许） |
| 储存条件 | Inert atmosphere,2-8°C |
| 酸度系数(pKa) | 13.33±0.70(Predicted) |
| 属性 | 值 |
|---|---|
| 警示词 | 警告 |
| 防范说明 | P261-P305+P351+P338 |
| 危险性描述 | H302-H315-H319-H335 |
| 危险性符号(GHS) | GHS07 |
| 标题 | 内容 |
|---|---|
| 靶点 | Target Value RET () KDR () c-Kit () c-Abl () FLT3 (Cell-free assay) 0.12 μM(Ki) |
| 体内研究 | After a single oral administration of 15 mg/kg of AST 487 to OF1 mice, a mean peak plasma level (C max ) of 0.505±0.078 μM SE is achieved after 0.5 h. Similar levels of AST 487 are found in the plasma of mice up to 6 h after oral administration, with a C last of 21±4 nM at 24 h. The oral bioavailability is calculated to be 9.7% with a t 1/2 terminal elimination of 1.5 h. |
| 体外研究 | A number of other kinases are also similarly inhibited by AST 487 (NVP-AST487) in the in vitro kinase assays, including KDR (IC 50 =170 nM), Flt-4 (IC 50 =790 nM), Flt-3 (IC 50 =520 nM), c-Kit (IC 50 =500 nM), and c-Abl (IC 50 =20 nM). AST 487 potently inhibits the growth of human thyroid cancer cell lines with activating mutations of RET but not of lines without RET mutations. Both GDNF/GFRα1 and persephin-induced calcitonin mRNA are markedly inhibited by coincubation with 100 nM of AST 487 in MTC-M cells. AST 487 is a novel, mutant FLT3 inhibitor. AST 487 is tested in biochemical assays for inhibition of Flt-3 kinase activity. The K i is determined to be 0.12 μM. Besides Flt-3, NVP-AST487 inhibits RET, KDR, c-Kit, and c-Abl kinase with IC 50 values below 1 μM. Treatment of FLT3-ITD-Ba/F3 cells and D835Y-Ba/F3 cells with AST 487 potently inhibits cellular proliferation (IC 50 <5 nM). AST 487 treatment of FLT3-ITD-Ba/F3 cells with 0.01 μM AST 487 results in complete cell killing compare with approximately 50% killing of AML patient samples at the same concentration. |
| 生物活性 | AST-487 (NVP-AST487)，一种N,N'-二苯基脲，是Flt3的竞争性抑制剂，ki值为0.12 μM。除FLT3以外，AST487还抑制RET,KDR,c-KIT 和 c-ABL 激酶，IC50值低于1 μM。 |