4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮

制备生物活性体外研究体内研究 4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮试剂级价格

CAS号:1162656-22-5
英文名:MCB-613
中文名:4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮
CBNumber:CB03049202
分子式:C20H20N2O
分子量:304.39
MOL File:1162656-22-5.mol

4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮化学性质

沸点 :510.4±50.0 °C(Predicted)
密度 :1.159±0.06 g/cm3(Predicted)
储存条件 :Sealed in dry,Room Temperature
溶解度 :insoluble in H2O; ≥13.2 mg/mL in DMSO with gentle warming; ≥9.26 mg/mL in EtOH with ultrasonic
形态 :solid
酸度系数(pKa) :4.36±0.12(Predicted)
颜色 :Light yellow to yellow

4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮性质、用途与生产工艺

制备以3-吡啶甲醛及对乙基环己酮为原料，通过Claisen-Schmidt缩合反应得到双吡啶α,β-不饱和酮中间体4-乙基-2,6-双(吡啶-3-基亚甲基)环己酮。采用干燥的HCl作为缩合反应的催化剂，操作简便，产率较高，均在85％以上。
生物活性 MCB-613 是一种有效的类固醇受体共激活因子 (SRC) 小分子“刺激物” (SMS)，超刺激 SRCs 的转录活性。 MCB-613 增加了 SRC 与其他共激活因子的相互作用，并显着诱导 ER 应激与活性氧 (ROS) 的产生相结合。 MCB-613 是一种 SMS，通过过度刺激 SRC 致癌程序，靶向癌基因用作抗癌药物。

体外研究

MCB-613 (6-8 μM; 24 hours) activates endogenous MMP13 mRNA expression in MDA-MB-231 cells. MCB-613 (2-10 μM; 4 hours) leads to proteasome dysfunction and ER stress, the induction of the markers for unfolded protein response (UPR), including the phosphorylation of eIF2α and IRE1α as well as the induction of ATF4 protein expression. MCB-613 (0-7 μM; 4 hours) affects SRC-3 KO and WT HeLa cell viability, SRC-3 WT HeLa cell is more affected by MCB-613 compared with KO cells.

RT-PCR

Cell Line:	MDA-MB-231 cells
Concentration:	6 μM; 8 μM
Incubation Time:	24 hours
Result:	Increased MMP13 mRNA expression.

Western Blot Analysis

Cell Line:	HeLa cells
Concentration:	2 μM; 4 μM; 6 μM; 8 μM; 10 μM
Incubation Time:	24 hours
Result:	Induced the p-eIF2α, p-IRE1α, and ATF-4 protein expression.

Cell Viability Assay

Cell Line:	SRC-3 KO and WT HeLa cells
Concentration:	3 μM; 4 μM; 5 μM; 6 μM; 7 μM
Incubation Time:	24 hours
Result:	Decreased SRC-3 KO and WT HeLa cell viability.

体内研究

MCB-613 (intravenous injection; 20 mg/kg; 3 times/week; 7 weeks) significantly and dramatically stalls the growth of the tumor compared with the control group and causes no obvious animal toxicity

Animal Model:	MCF-7 breast cancer mouse xenograft model (athymic nude mice by injecting MCF-7 cells into mammary fat pads)
Dosage:	20 mg/kg
Administration:	Intravenous injection; 20 mg/kg; 3 times/week; 7 weeks
Result:	Inhibited tumor growth in vivo.