巴多昔芬

中文名称:

巴多昔芬

中文同义词:

巴多昔芬中间体;巴多昔芬;巴佐昔芬杂质;巴多兮芬;1-[[4-[2-(氮杂环庚烷-1-基)乙氧基]苯基]甲基]-2-(4-羟基苯基)-3-甲基-吲哚-5-醇;1-(4-(2-(氮杂环庚烷-1-基)乙氧基)苄基)-2-(4-羟基苯基)-3-甲基-1H-吲哚-5-醇

英文名称:

Bazedoxifene

英文同义词:

CS-1993;Batoxifene;1-[[4-[2-(azepan-1-yl)ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methyl-indol-5-ol;1-((4-(2-Hexahydro-1H-azepin-1-yl)ethoxy)phenyl)methyl)-2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol;1H-Indol-5-ol, 1-((4-(2-(hexahydro-1H-azepin-1-yl)ethoxy)phenyl)methyl)-2-(4-hydroxyphenyl)-3-methyl-;Bazedoxifene;Bazedoxifene [inn];Bazedoxifeno

CAS号:

198481-32-2

分子式:

C30H34N2O3

分子量:

470.6

EINECS号:

805-732-1

相关类别:

原料药标样;G蛋白偶联受体G蛋白;医药中间体;中间体;原料药;医药原料;Aromatics;Heterocycles;Intermediates Fine Chemicals;Pharmaceuticals

Mol文件:

198481-32-2.mol

熔点 

98-102°

沸点 

694.4±55.0 °C(Predicted)

密度 

1.19

酸度系数(pKa)

10.12±0.15(Predicted)

生物活性

Bazedoxifene (TSE-424) 是一种有口服活性的，能透过血脑屏障的，非甾体、选择性的雌激素受体调节剂 (SERM)，对 ERα 和 ERβ 作用的 IC50 值分别为 26 nM 和 99 nM，可用于骨质疏松症的研究。Bazedoxifene 也是一种 IL-6/GP130 蛋白相互作用抑制剂，可用于胰腺癌的研究。

靶点

IC50: 26 nM (ERα), 99 nM (ERβ)

体外研究

Bazedoxifene is a small molecular GP130 inhibitor, which binds to GP130 D1 domain. Bazedoxifene inhibits STAT3 phosphorylation induced by Il-6 and IL-11 in GP130/STAT3 pathway signaling. Bazedoxifene (10 μM-20 μM; 2 hours) inhibits STAT3 Phosphorylation Induced by cytokines in human pancreatic cancer cells. Bazedoxifene (5-20 μM; overnight) induces apoptosis in human pancreatic cancer cells. Bazedoxifene inhibits STAT3 nuclear translocation induced by IL-6. Bazedoxifene blocks the cells migration in pancreatic cancer cells by inhibition of GP130. Western Blot Analysis Cell Line: AsPC-1 cells Concentration: 10 μM, 20 μM Incubation Time: 2 hours Result: Inhibited IL-6, IL-11 or OSM (50 ng/mL) induced STAT3 phosphorylation. Apoptosis Analysis Cell Line: Capan-1 cells, BxPC-3 cells, HPAF-II cells, HPAC cells Concentration: 10 μM, 20 μM (Capan-1); 5 μM, 10 μM (BxPC-3); 10 μM, 20 μM (HPAF-II); 10 μM, 15 μM (HPAC) Incubation Time: Overnight Result: Induced apoptosis.

Cell Line:

AsPC-1 cells

Concentration:

10 μM, 20 μM

Incubation Time:

2 hours

Result:

Inhibited IL-6, IL-11 or OSM (50 ng/mL) induced STAT3 phosphorylation.

Cell Line:

Capan-1 cells, BxPC-3 cells, HPAF-II cells, HPAC cells

Concentration:

10 μM, 20 μM (Capan-1); 5 μM, 10 μM (BxPC-3); 10 μM, 20 μM (HPAF-II); 10 μM, 15 μM (HPAC)

Incubation Time:

Overnight

Result:

Induced apoptosis.

体内研究

Bazedoxifene (5 mg/kg; i.g.; daily, for 18 days) inhibits Capan-1 tumor growth in mouse model in vivo. Animal Model: 6-week-old female athymic nude mice Dosage: 5 mg/kg Administration: Oral gavage, daily, for 18 days Result: Suppressed pancreatic cancer xenograft tumor growth and induced apoptosis in tumor cells.

Animal Model:

6-week-old female athymic nude mice

Dosage:

5 mg/kg

Administration:

Oral gavage, daily, for 18 days

Result:

Suppressed pancreatic cancer xenograft tumor growth and induced apoptosis in tumor cells.