AST 487
中文名称 | AST 487 |
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中文同义词 | 1-(4-((4-乙基哌嗪-1-基)甲基)-3-(三氟甲基)苯基)-3-(4-((6-(甲基氨基)嘧啶-4-基)氧基)苯基)脲;化合物AST 487;N-[4-[(4-ETHYL-1-PIPERAZINYL)METHYL]-3-(TRIFLUOROMETHYL)PHENYL]-N'-[4-[[6-(METHYLAMINO)-4-PYRIMIDINYL]OXY]PHENYL]UREA;RET激酶抑制剂(AST 487) |
英文名称 | AST 487 |
英文同义词 | AST 487;NVP-AST 487;1-{4-[(4-Ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl}-3-(4-{[6-(methylamino)-4-pyrimidinyl]oxy}phenyl)urea;1-(4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-(4-((6-(methylamino)pyrimidin-4-yl)oxy)phenyl)urea;AST487 (NVP- AST487);N-[4-[(4-Ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-N'-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea;Urea,N-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-N'-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]-;CS-562 |
CAS号 | 630124-46-8 |
分子式 | C26H30F3N7O2 |
分子量 | 529.56 |
EINECS号 | 205-525-8 |
相关类别 | 标准品;细胞生物学试剂 |
Mol文件 | 630124-46-8.mol |
结构式 |
AST 487 性质
熔点 | 162-164°C |
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沸点 | 563.1±50.0 °C(Predicted) |
密度 | 1.341±0.06 g/cm3(Predicted) |
储存条件 | under inert gas (nitrogen or Argon) at 2-8°C |
溶解度 | 可溶于DMSO(少许)、甲醇(少许) |
酸度系数(pKa) | 13.33±0.70(Predicted) |
形态 | 固体 |
颜色 | 白色至浅黄色至浅橙色 |
Target | Value |
RET
() | |
KDR
() | |
c-Kit
() | |
c-Abl
() | |
FLT3
(Cell-free assay) | 0.12 μM(Ki) |
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.
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.
安全信息
更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
---|---|---|---|---|---|
2024/08/19 | HY-15002 | AST 487 | 1 mg | 360元 | |
2024/08/19 | HY-15002 | AST 487 AST 487 | 630124-46-8 | 5mg | 900元 |