6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐
生物活性靶点体外研究体内研究
| 中文名称 | 6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 | 
|---|---|
| 中文同义词 | 6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐;PD 166285 双盐酸盐;化合物 PD0166285 DIHYDROCHLORIDE | 
| 英文名称 | PD 166285 | 
| 英文同义词 | 6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one Hydrochloride;PD 166285;PD 166285 - CAS 212391-63-4 - Calbiochem;6-(2,6-dichlorophenyl)-2-[4-[2-(diethylamino)ethoxy]anilino]-8-methylpyrido[2,3-d]pyrimidin-7-one,dihydrochloride;6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimidin-7(8H)-onedihydrochloride;PD 166285 dihydrochloride;6-(2,6-Dichloro-phenyl)-2-[4-(2-diethylaMino-ethoxy)-phenylaMino]-8-Methyl-8H-pyrido[2,3-d]pyriMidin-7-one hydrochloride;6-(2,6-Dichlorophenyl)-2-[[4-[2-(diethylamino)ethoxy]phenyl]amino]-8-methylpyrido[2,3-d]pyrimi | 
| CAS号 | 212391-63-4 | 
| 分子式 | C26H29Cl4N5O2 | 
| 分子量 | 585.37 | 
| EINECS号 | |
| 相关类别 | Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators | 
| Mol文件 | 212391-63-4.mol | 
| 结构式 | ![6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 结构式](https://yunshiji.oss-cn-shenzhen.aliyuncs.com/202410/29/1350355318800000199.gif) | 
6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 性质
| 熔点 | 239-242?C | 
|---|---|
| 储存条件 | Desiccate at RT | 
| 溶解度 | 可溶于二甲基亚砜、甲醇 | 
| 形态 | 淡黄色固体 | 
| 颜色 | 粘黄色 | 
| 稳定性 | 吸湿性 | 
6-(2,6-二氯苯基)-2-[[4-[2-(二乙基氨基)乙氧基]苯基]氨基]-8-甲基吡啶并[2,3-D]嘧啶-7(8H)-酮盐酸盐 用途与合成方法
生物活性
PD0166285 dihydrochloride是 P-gp 的一个底物,是 WEE1 抑制剂,也可微弱抑制 Myt1,IC50 值分别为 24 和 72 nM。PD0166285 dihydrochloride 对 Chk1 的 IC50 值为3.433 μM。
靶点
IC50: 24 nM (WEE1), 72 nM (Myt1), 3.433 μM (Chk1).
体外研究
PD0166285 (0.5 μM) dramatically inhibits irradiation-induced Cdc2 phosphorylation at the Tyr-15 and Thr-14 in seven of seven cancer cell lines.  
  PD0166285 sensitizes radiation-induced cell killing in p53 mutant HT29 cells and in the E6-transfected, p53-null ovarian cancer cell line PA-1 but to a lesser extent in p53 wild-type PA-1 cells. PD0166285 abrogates irradiation-induced G2 arrest and significantly increases mitotic cell populations.  
  PD0166285 acts as a radiosensitizer to sensitize cells to radiation-induced cell death with a sensitivity enhancement ratio of 1.23.  
 
Western Blot Analysis
| Cell Line: | Human and mouse cancer cell lines (HCT116, HT29, DLD-1, HCT8, H460, HeLa, C 26). | 
| Concentration: | 0.5 μM. | 
| Incubation Time: | 4 h. | 
| Result: | Inhibited Cdc2Y15 and CdcT14 phosphorylation. | 
体内研究
| Animal Model: | Wild-type, Abcg2 -/- , Abcb1a/b -/- and Abcb1a/b;Abcg2 -/- FVB mice. | 
| Dosage: | 5 mg/kg. | 
| Administration: | IV. | 
| Result: | C         max        is about 400 ng/mL. P-gp, but not BCRP, limited the brain penetration of PD0166285. | 

 
 

 





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