667880-38-8

中文名称 5-({1-[2-(2,4-dimethylphenoxy)ethyl]-2-methyl-1H-indol-3-yl}methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

英文名称 5-({1-[2-(2,4-dimethylphenoxy)ethyl]-2-methyl-1H-indol-3-yl}methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

CAS 667880-38-8

分子式 C24H23N3O3S

分子量 433.523

MOL 文件 667880-38-8.mol

更新日期 2023/03/13 18:03:56

667880-38-8 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物ZLDI-8

英文别名

IAC-8
5-({1-[2-(2,4-dimethylphenoxy)ethyl]-2-methyl-1H-indol-3-yl}methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione

物理化学性质

密度1.30±0.1 g/cm3(Predicted)

储存条件-20°C储存

溶解度62.5 mg/mL in DMSO

酸度系数(pKa)5.34±0.20(Predicted)

形态Solid

颜色Yellow to orange

常见问题列表

生物活性

ZLDI-8 是一种 Notch 活化/裂解酶 ADAM-17 抑制剂，可抑制 Notch 蛋白的裂解，并降低促存活/抗凋亡和上皮-间质转化相关蛋白的表达。ZLDI-8 还是一种竞争性和不可逆的酪氨酸磷酸酶 (Lyp) 抑制剂，IC50 为 31.6 μM，Ki 为 26.22 μM。ZLDI-8 以 IC50 为 5.32 μM 抑制 MHCC97-H 细胞的生长。

靶点

ADAM-17
IC50: 31.6 μM (Tyrosine phosphatase)
Ki: 26.22 μM (Tyrosine phosphatase)

体外研究

ZLDI-8 (0.03-30 μM; 6-72 hours; MHCC97-H cells) treatment reduces cell viability in a time- and dose-dependent manner.
ZLDI-8 (1-10 μM; 6-72 hours; MHCC97-H cells) significantly decreases the level of NICD and the accumulation of NICD in the nucleus. ZLDI-8 could also reduce the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2. And also increases the expression of epithelial marker E-Cadherin and reduced mesenchymal markers N-Cadherin and Vimentin.
ZLDI-8 enhances chemotherapy effects on tumor cell proliferation blockage, induction of apoptosis and cell-cycle arrest by inhibiting Notch pathway and blocking chemical resistance.

Cell Viability Assay

Cell Line:	MHCC97-H cells
Concentration:	0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, 30 μM
Incubation Time:	6 hours, 12 hours, 24 hours, 48 hours, 72 hours
Result:	Emerged cytotoxic effect on MHCC97-H cells in a time- and dose-dependent manner.

Western Blot Analysis

Cell Line:	MHCC97-H cells
Concentration:	1 μM, 3 μM, 10 μM
Incubation Time:	6 hours, 12 hours, 24 hours, 48 hours, 72 hours
Result:	Significantly decreased the level of NICD and the accumulation of NICD in the nucleus. Also reduced the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2

体内研究

ZLDI-8 (0.2-2 mg/kg; intraperitoneal injection; every two days; for 20 days; nude mice) treatment enhances the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model.

Animal Model:	Nude mice with MHCC-97H cells
Dosage:	2 mg/kg, 1 mg/kg, 500 μg/kg, or 200 μg/kg
Administration:	Intraperitoneal injection; every two days; for 20 days
Result:	Inhibited tumor growth in nude HCC-bearing mice model.