(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮

简介合成方法生物活性体外研究体内研究 (2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮试剂级价格

CAS号:176957-55-4
英文名:Cyclopentanone, 2,5-bis(2-thienylMethylene)-, (E,E)-
中文名:(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮
CBNumber:CB92682247
分子式:C15H12OS2
分子量:272.39
MOL File:176957-55-4.mol

(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮化学性质

熔点 :222-223℃
储存条件 :2-8°C
溶解度 :DMSO: >3mg/mL
形态 :powder, yellow
敏感性 :Light Sensitive

安全信息

危险品标志 :Xi
危险类别码 :36/37/38
安全说明 :26
WGK Germany :3

(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮性质、用途与生产工艺

简介
环戊酮曼尼希碱类化合物是由天然萜类化合物进行结构改造而设计合成的一类具有抗炎活性的化合物。构效关系研究显示二(2-噻吩基亚甲基)环戊酮曼尼希碱类化合物抗炎活性较强。(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮是其中代表性化合物。
合成方法以2-噻吩甲醛及环戊酮或N-环戊烯基吗啉为起始物料，经曼尼希反应制备得到目标化合物(2E,5E)-2,5-二(2-噻吩基亚甲基)环戊酮。其合成反应式如下图：
生物活性 CCT007093 是有效的蛋白磷酸酶 1D (PPM1D Wip1) 的抑制剂。Wip1 的抑制可激活mTORC1 通路，增强肝切除手术后肝细胞的增殖。

体外研究

CCT007093 (25 or 50 µM, 8 h) significantly increases the phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159, and the phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) are also up-regulated in transfected HEK293T cell line.
CCT007093 shows specificity for MCF-7 cells, reducing viability by 40% after 2 days with no observable effect on the growth of HeLa cells.
CCT007093 induces P38 phosphorylation at 4 h post exposure in MCF-7 cells (sensitive to PPM1D inhibition), and does not induce P38 phosphorylation in HeLa cells (relatively resistant to PPM1D inhibition).

Western Blot Analysis

Cell Line:	HEK293T cell line.
Concentration:	25 or 50 µM.
Incubation Time:	8 h.
Result:	The phosphorylation levels of mTOR at Ser2448, Ser2481 and Ser2159 were all significantly increased ^[1] . The phosphorylation levels of p70S6K (Thr389) and S6 (Ser235/236) were also up-regulated ^[1] .

体内研究

CCT007093 (6.4 mg/kg) enhances liver regeneration and increases the survival rate of mice following major hepatectomy.

Animal Model:	Wild-type mice.
Dosage:	3.2 and 6.4 mg/kg.
Administration:	Injected intraperitoneally 4 times (mice were sacrificed at 36 h post-PH).
Result:	Significantly improved survival in mice following major hepatectomy (80% hepatectomy). The level of PCNA was also significantly increased in the liver of CCT007093-treated mice at 36h, 48h and 72h post-PH.